Image guidance methods and apparatus for glaucoma surgery

ABSTRACT

An imaging probe comprises a camera or endoscope with an external detector array, in which the probe is sized and shaped for surgical placement in an eye to image the eye from an interior of the eye during treatment. The imaging probe and a treatment probe can be coupled together with a fastener or contained within a housing. The imaging probe and the treatment probe can be sized and shaped to enter the eye through an incision in the cornea and image one or more of the ciliary body band or the scleral spur. The treatment probe may comprise a treatment optical fiber or a surgical placement device to deliver an implant. A processor coupled to the detector can be configured with instructions to identify a location of one or more of the ciliary body band, the scleral spur, Schwalbe&#39;s line, or Schlemm&#39;s canal from the image.

RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.17/303,811, filed Jun. 8, 2021, which is a continuation of U.S. patentapplication Ser. No. 17/248,543, filed Jan. 28, 2021, which is acontinuation of International Patent Application No. PCT/US2020/040558,filed Jul. 1, 2020, which published as WO 2021/003304 on Jan. 7, 2021,which claims the benefit under 35 U.S.C. § 119(e) of U.S. ProvisionalPatent Application No. 62/869,267 filed on Jul. 1, 2019, and U.S.Provisional Patent Application No. 62/994,181, filed on Mar. 24, 2020,the entire disclosures of which are incorporated herein by reference.

The subject matter of the present application is also related toInternational Application No. PCT/US2018/038072, filed Jun. 18, 2018,entitled “Methods and Systems for OCT Guided Glaucoma Surgery”,published as WO 2018/232397, the entire disclosure of which isincorporated herein by reference.

BACKGROUND

The prior methods and apparatus for treating diseases such as diseasesof the eye can be less than ideal in at least some respects. One exampleof a disease that can be difficult to treat is glaucoma. Although sometreatments can be successful, the prior approaches to treating glaucomacan be less than ideal in a least some respects. One approach to treatglaucoma is with minimally invasive glaucoma surgery (“MIGS”). Withcanal based MIGS, a small opening is formed in the trabecular meshworkto allow fluid to drain into Schlemm's canal. These openings can beformed in many ways, for example with implants or lasers. One approachhas been to use excimer laser trabeculostomy (“ELT), in which anultraviolet laser such as an excimer laser is used to ablate an openingin the trabecular meshwork into Schlemm's canal. Another approach hasbeen to place an implant that extends through the trabecular meshworkinto Schlemm's canal. One potentially challenging aspect of canal basedMIGS procedures is alignment of a surgical instrument with Schlemm'scanal, which can be approximately 200 micrometers (“μm”) to 400 μm. Insome instances, Schlemm's canal may not be readily visible, and thesurgeon may try to estimate the location of Schlemm's canal, which canbe challenging and less than ideally accurate in at least someinstances. With some implantation procedures, in accurate assessment ofthe location of Schlemm's canal can lead to the implant not being fullyplaced in the canal, may lead to tearing of the trabecular meshwork, andin some instances the implant can become dislodged, for example.

With normal ocular pressure, Schlemm's canal is typically not visiblefrom an internal view with a camera. When pressure of the eye issufficiently low, blood can enter Schlemm's canal and improvevisualization of Schlemm's canal. However, once the trabecular meshworkhas been penetrated, blood from Schlemm's canal can enter the anteriorchamber of the eye, making visualization of the trabecular meshwork moredifficult than would be ideal.

In light of the above, it would be beneficial to have improved methodsand apparatus to assist the surgeon in identifying the location ofSchlemm's canal to facilitate the formation of openings in Schlemm'scanal and the placement of implants.

SUMMARY

In some embodiments, a probe comprises a treatment probe comprising atreatment element and an imaging probe to image the treatment elementand the anatomic structures targeted for treatment and adjacentstructures from an interior of the eye. In some embodiments, thetreatment element comprises one or more of an optical fiber or animplant. In some embodiments, a probe comprises a camera sized andshaped for surgical placement in an eye and a treatment probe. In someembodiments, an elongate imaging probe comprises the camera, whichcomprises one or more lenses and a detector sized for placement in theeye. Alternatively, or in combination, the imaging probe may compriseone or more lenses and one or more optical fibers such as an array ofoptical fibers or a scanning optical fiber arranged to transmit animage. In some embodiments, the treatment probe and the imaging probeare coupled to each other, such as with a fastener, so as to fix arotational angle between an elongate axis of the imaging probe and thetreatment probe. In some embodiments, the camera and the treatment probeare enclosed together in a housing. The camera and treatment probe aresized and shaped to enter the eye through an incision in the cornea andimage one or more of the ciliary body band, the scleral spur, thetrabecular meshwork, the juxtacanalicular trabecular meshwork, Schlemm'sCanal, the inner wall of Schlemm's Canal, compression of the trabecularmeshwork, sites of collector channel orifices where visible from withinthe anterior chamber, iris root, and other intraocular structures. Thetreatment probe may comprise an optical fiber or a surgical placementdevice to deliver an implant. A detector of the camera is sized andshaped for placement in the eye and coupled to a processor configuredwith instructions to identify a location of one or more of the ciliarybody band, the scleral spur, Schwalbe's line, or Schlemm's canal fromthe image.

In some embodiments, an optical fiber coupled to the camera comprises aninclined distal end, and the processor is configured with instructionsto determine an orientation of the inclined end in response to the imagefrom the camera. The processor can be configured with instructions todisplay markers corresponding to locations of one or more of the irisroot, the ciliary body band, the scleral spur, Schwalbe's line, orSchlemm's canal and the treatment probe and other anatomiclandmarks/structures. The image from the camera and the markers can beprovided to the surgeon in many ways. In some embodiments, the imagefrom the camera placed in the eye is shown on a heads-up display of amicroscope, such as an operating microscope, which can allow the surgeonto view the eye anteriorly through a microscope and to view the image ofthe eye from the camera inserted into the eye, while viewing the imagesthrough the oculars of the microscope. In some embodiments, a secondcamera or cameras coupled to a microscope, such as an operatingmicroscope, provides a microscope image of the eye which is shown on aviewing device. The images from the second camera, the camera placed inthe eye, and the markers can be shown on the display, for example,sequentially or concurrently and updating with movement of the probe.These approaches can facilitate the surgery, and in some embodimentsallows the surgery to be performed without a gonioscope.

INCORPORATION BY REFERENCE

All patents, applications, and publications referred to and identifiedherein are hereby incorporated by reference in their entirety and shallbe considered fully incorporated by reference even though referred toelsewhere in the application.

BRIEF DESCRIPTION OF THE DRAWINGS

A better understanding of the features, advantages and principles of thepresent disclosure will be obtained by reference to the followingdetailed description that sets forth illustrative embodiments, and theaccompanying drawings of which:

FIG. 1 shows a schematic sectional view of an eye illustratinganatomical structures;

FIG. 2 shows a perspective partial view of the anatomy adjacent to theanterior chamber of an eye;

FIG. 3 shows a schematic sectional view of an eye illustrating a fiberoptic probe and imaging probe crossing the anterior chamber from acorneal limbal paracentesis site toward the trabecular meshwork in theanterior chamber of the eye in accordance with some embodiments;

FIG. 4A shows a partial schematic view of the anatomy of the anteriorchamber angle of an eye showing Schlemm's canal, the scleral spur andSchwalbe's line;

FIG. 4B shows a partial view of the anatomy of an eye and isrepresentative of an image obtained with an endoscope or other imagingsystem from the viewpoint of within an eye;

FIG. 5A shows an exemplary image overlaid with markers in accordancewith some embodiments with the probe rotated with respect to the targettissue;

FIG. 5B shows an exemplary image as in FIG. 5A in accordance with someembodiments with the probe rotationally aligned with the target tissue;

FIG. 6A shows an exemplary image overlaid with treatment markers inaccordance with some embodiments with the implantation axis of theimplant rotated with respect to Schlemm's canal;

FIG. 6B shows an exemplary image overlaid with markers showing animplantation axis of the implant aligned with Schlemm's canal inaccordance with some embodiments;

FIG. 7 shows an apparatus for eye surgery in accordance with someembodiments;

FIG. 8 shows an augmented image comprising an optical operatingmicroscope view and an internal camera view overlaid with treatmentmarkers;

FIG. 9A shows placement of an implant in accordance with someembodiments;

FIG. 9A-1 shows an implant comprising an engagement structure sized andshaped to receive a protrusion of the inserter so as to fix the angle ofelongate axis of the implant with the axis of the camera.

FIG. 9B shows an instrument for placement of an implant in Schlemm'scanal and placement of implants in Schlemm's canal in accordance withsome embodiments;

FIG. 10 shows an example of a treatment probe and a camera in accordancewith some embodiments;

FIG. 11 shows a cross sectional schematic view of an example treatmentprobe and camera taken along the line A-A from FIG. 10 in accordancewith some embodiments;

FIG. 12A shows an example of a treatment probe and a camera inaccordance with some embodiments;

FIG. 12B shows a cross sectional schematic view of an example treatmentprobe and camera taken along the line B-B of FIG. 12A in accordance withsome embodiments;

FIG. 13 shows an example of a treatment probe and a camera in accordancewith some embodiments;

FIG. 14 is a flowchart diagram showing methods in accordance with someembodiments;

FIG. 15 shows an apparatus for eye surgery in accordance with someembodiments;

FIG. 16 shows an example of a treatment probe and a fiber optic arraycoupled to each other with a fastener, in accordance with someembodiments;

FIG. 17 shows a cross sectional schematic view of an example treatmentprobe and fiber optic array taken along the line A-A from FIG. 16 inaccordance with some embodiments;

FIG. 18A shows an example of a treatment probe and a fiber optic arraywith an integrated housing in accordance with some embodiments;

FIG. 18B shows a cross-sectional schematic view of an example treatmentprobe and camera taken along the line B-B of FIG. 18A; and

FIG. 19 shows an example of a treatment probe and a fiber optic array inaccordance with some embodiments; and

FIG. 20 shows an example of a treatment probe and a fiber optic array inaccordance with some embodiments.

DETAILED DESCRIPTION

The following detailed description and provides a better understandingof the features and advantages of the inventions described in thepresent disclosure in accordance with the embodiments disclosed herein.Although the detailed description includes many specific embodiments,these are provided by way of example only and should not be construed aslimiting the scope of the inventions disclosed herein.

Methods and systems disclosed herein can allow more ophthalmic surgeonsto successfully perform MIGS procedures. For example, the disclosedmethods and apparatus can allow for surgeries to more uniformly andconsistently create openings to enable improved outflow of aqueous fluidfrom the eye's anterior chamber into Schlemm's canal, for example. Inaddition, the disclosed system and methods can lead to improved surgicaloutcomes, by allowing surgeons to identify target locations for openingsinto Schlemm's canal intended to increase outflow. In some cases, atarget location may include a surface or layer of a tissue, or aposition at a tissue, for example of the trabecular meshwork, thejuxtacanalicular trabecular meshwork (JCTM), the inner wall of theSchlemm's canal, the outer wall of the Schlemm's canal, the sclera, ordesired combinations thereof.

The presently disclosed methods and apparatus may include thecombination of a microscope, such as a surgical microscope, image withsensing devices which enable real-time display images to be concurrentlyviewed by the surgeon. The real-time display image includes an imagewhich is updated during procedures with minimal latencies. For practicalpurposes, the real-time augmented display shows images, including video,as events are happening. These augmented images enable the surgeon toview, target and treat locations within an eye which may not be readilyvisualized using the operating microscope alone, due to their locationwithin the eye at sites in which total internal reflections precludestheir visualization in the microscope image, unaided. Such structuresinclude the trabecular meshwork and Schlemm's canal. The methods andapparatus disclosed herein enable a surgeon to view angle structuresthat are obscured or blocked by total internal reflection. For example,the disclosed methods and apparatus can allow images or information ofthose otherwise poorly visible or non-visible structures, such as thecollector channel system, to be visualized using a camera inserted intothe eye, such as by using endoscopic camera technologies. A surgeon canconcurrently view a real image of the eye with an overlying projectedimage of ocular structures by the placement of an image of thosestructures, such as the collector channel system via, for example, animaging system placed adjacent the treatment probe, which may beobtained earlier than a surgery, or which may be obtained in real-timeduring the surgery which may be registered to visible structures ormarkers, to enable the surgeon to identify and target preferred surgicalsites. In this manner, the images viewed by the surgeon include real(optical) and projected (virtual) images combined on a display toenhance surgical visualization and targeting treatment of such tissues.

In some embodiments, the endoscope comprises imaging optics to form animage of the target tissue on an external sensor array, such as a sensorarray located on a handpiece of the probe or a sensor array located on aconsole of a surgical workstation. In embodiments comprising a sensorarray located outside the eye, the endoscope may comprise one or moreoptical fibers, e.g. a plurality of optical fibers, to transmit an imageto the sensor array located outside the eye. In some embodiments, animage of the eye is formed on one or more ends of one or more opticalfibers located within the eye and the image is transmitted via the oneor more optical fibers to the sensor array located outside the eye.Alternatively, the endoscope may comprise a camera comprising the sensorarray, in which the camera is inserted into the eye as described herein.

The images from either or both the microscope and the endoscope can bepresented to the surgeon in many ways. For example, the images can besuperimposed on an image viewed via a monitor or similar viewingdevices, such as augmented reality glasses, or goggles or virtualreality glasses or goggles. In some embodiments, a real-time image froma camera inserted into the eye is presented on a binocular heads updisplay with an optical image of the eye from an microscope, such as anoperating microscope, which allows the surgeon to view both the opticalimage and image from the camera while looking into the microscope. Insome embodiments these images are registered to each other with commonelements enabling positioning of the intraocular camera system imagerelative to the microscope image. Additional information can also beprovided to the surgeon, such as virtual images of otherwise non-visiblestructures and one or more symbols to indicate both distances andmovement, such as from a probe tip to trabecular meshwork to Schlemm'scanal. In some embodiments, an in-situ camera can be used to identifycollector channels of the eye, and enable the surgeon to identify sitesby these target locations (e.g. by using a graphical visual element suchas a treatment reference marker to identify a target location) displayedto the user to assist in the creation of openings at appropriatelocations in the trabecular meshwork to increase flow. Some embodimentsof the present disclosure encompass any of a variety of in-eye imagingmodalities, including pre-operative and/or intra-operative images of theoutflow system (e.g. Schlemm's canal and collector channels), which canbe overlaid onto a microscope image or view. Further, image analysisalgorithms can be applied to recognize anatomical features within theeye during surgery and a heads-up display can augment the real-timeimaging with recognized features, guides, locations, markers, and thelike to assist the surgeon in completing the surgery. In some cases, oneor more images captured by an imaging sensor located within the eye canbe used to generate a virtual image of the angle structures.

Such displays can be coupled to the operating microscope in order topresent monocular or binocular virtual and/or augmented images from adisplay which is visually combined with binocular real optical images ofthe eye, for example. The methods and apparatus disclosed herein arewell suited for utilization with ELT surgery and with an implant devicesuch as stent surgeries which provide openings to drain fluid from theeye. However, the provided system and methods can also be applied tovarious other surgical procedures where fiberoptic-based imaging may beutilized, e.g. any and all surgeries using an endoscope.

In some embodiments, the endoscope comprises a stereoscopic endoscopeconfigured to provide the user with a stereoscopic image of thetreatment element from an interior of the eye. The display may comprisea stereoscopic image display to provide the user with a stereoscopicimage of the treatment element to facilitate surgeries within the eye.

Although specific reference is made to the treatment of glaucoma usingexcimer laser trabeculostomy (“ELT”), the methods and systems disclosedherein can be used with many other types of surgeries. For example, theembodiments disclosed herein can be used with other surgical procedures,including endoscopic procedures relating to orthopedic, neurosurgical,neurologic, ear nose and throat (ENT), abdominal, thoracic,cardiovascular, epicardial, endocardial, and other applications to namea few. The presently disclosed methods and apparatus can utilize in-situimaging to improve targeting accuracy and provide virtual visualizationfor enabling surgeons to perform procedures in regions that may not bereadily visualized either microscopically or endoscopically. Suchapplications include any endoscopic procedure in which virtualvisualization is augmented to real images to assist surgical accuracy in3-dimensional space, one example of which is an endovascular procedurein which the vessel curves or bends. As used herein, the term “in-situ”,as related to imaging, refers to an imaging sensor, such as any numberof suitable camera systems, that is positioned at or in close proximityto the treatment site. In some cases, an in-situ imaging system iscarried by or with the treatment probe and captures images from thetreatment site or along the path to the treatment site to allow thesurgeon to see actual anatomical features.

Certain aspects may also be used to treat and modify other organs suchas brain, heart, lungs, intestines, skin, kidney, liver, pancreas,stomach, uterus, ovaries, testicles, bladder, ear, nose, mouth, softtissues such as bone marrow, adipose tissue, muscle, glandular andmucosal tissue, spinal and nerve tissue, cartilage, hard biologicaltissues such as teeth, bone, as well as body lumens and passages such asthe sinuses, ureter, colon, esophagus, lung passages, blood vessels, andthroat. For example, the devices disclosed herein may be insertedthrough an existing body lumen or inserted through an opening created inbody tissue.

With reference to FIG. 1, in order to appreciate the describedembodiments, a brief overview of the anatomy of the eye E is provided.As schematically shown in FIG. 1, the outer layer of the eye includes asclera 17. The cornea 15 is a transparent tissue which enables light toenter the eye. An anterior chamber 7 is located between the cornea 15and an iris 19. The anterior chamber 7 contains a constantly flowingclear fluid called aqueous humor 1. The crystalline lens 4 is supportedand moved within the eye by fiber zonules, which are connected to theciliary body 20. The iris 19 is attached circumferentially to thescleral spur and includes a central pupil 5. The diameter of the pupil 5controls the amount of light passing through the lens 4 to the retina 8.A posterior chamber 2 is located between the iris 19 and the ciliarybody 20.

As shown in FIG. 2 the anatomy of the eye further includes a trabecularmeshwork (TM) 9, a triangular band of spongy tissue within the eye thatlies anterior to the iris 19 insertion to the scleral spur. The mobiletrabecular meshwork varies in shape and is microscopic in size. It isgenerally triangular in cross-section, varying in thickness from about100-200 μm. It is made up of different fibrous layers havingmicron-sized pores forming fluid pathways for the egress of aqueoushumor from the anterior chamber. The trabecular meshwork 9 has beenmeasured to about a thickness of about 100 μm at its anterior edge,Schwalbe's line 18, at the approximate juncture of the cornea 15 andsclera 17.

The trabecular meshwork widens to about 200 μm at its base where it andiris 19 attach to the scleral spur. The height of the trabecularmeshwork can be about 400 μm. The passageways through the pores intrabecular meshwork 9 lead through a very thin, porous tissue called thejuxtacanalicular trabecular meshwork 13, which in turn abuts theinterior wall of a vascular structure, Schlemm's canal 11. The height ofSchlemm's canal can be about 200 μm, or about half the height of thetrabecular meshwork. Schlemm's canal (SC) 11 is filled with a mixture ofaqueous humor and blood components and connects to a series of collectorchannels (CCs) 12 that drain the aqueous humor into the venous system.Because aqueous humor 1 is constantly produced by the ciliary body andflows through the pupil into the anterior chamber from which it passesthrough pores in the TM and JCTM into the SC and aqueous veins, anyobstruction in the trabecular meshwork, the juxtacanalicular trabecularmeshwork, or Schlemm's canal, prevents the aqueous humor from readilyescaping from the anterior eye chamber. As the eye is essentially aclosed globe, this results in an elevation of intraocular pressurewithin the eye. Increased intraocular pressure can lead to damage of theretina and optic nerve, and thereby cause eventual blindness.

The obstruction of the aqueous humor outflow, which occurs in most openangle glaucoma (i.e., glaucoma characterized by gonioscopically readilyvisible trabecular meshwork), is typically localized to the region ofthe juxtacanalicular trabecular meshwork (JCTM) 13, located between thetrabecular meshwork 9 and Schlemm's canal 11, and, more specifically,the inner wall of Schlemm's canal.

When an obstruction develops, for example, at the juxtacanaliculartrabecular meshwork 13, intraocular pressure gradually increases overtime. Therefore, a goal of current glaucoma treatment methods is toprevent optic nerve damage by lowering or delaying the progressiveelevation of intraocular pressure.

With reference to FIG. 3, a side sectional view of the interior anatomyof a human eye E is shown with a treatment probe comprising fiber-opticprobe 23, and a camera 25 coupled to the probe inserted into the eye inaccordance with some embodiments. A small self-sealing paracentesisincision 14 is created in the cornea 15. The anterior chamber can bestabilized with either a chamber maintainer using liquid flows or aviscoelastic agent. Fiber-optic probe 23 and the camera 25 can then bepositioned and advanced through the incision 14 into the anteriorchamber 7 until a distal end of the fiber-optic probe 23 contacts andslightly compresses the desired target TM tissues.

Photoablative laser energy produced by laser unit 31 (shown in FIG. 7)is delivered from the distal end of fiber-optic probe 23 in contact tothe tissue to be ablated. The tissue to be ablated may include thetrabecular meshwork 9, the juxtacanalicular trabecular meshwork 13 andan inner wall of Schlemm's canal 11. An aperture in the proximal innerwall of Schlemm's canal 11 is created in a manner which does notperforate the distal outer wall of Schlemm's canal. In some embodiments,additional apertures are created in the target tissues. Thus, theresultant aperture or apertures are effective to restore relativelynormal rates of drainage of aqueous humor. The photoablative laserenergy may comprise one or more types of laser energy, such as visible,ultraviolet, near infrared, or infrared laser energy, and combinationsthereof. In some embodiments, the laser energy comprises 308 nm laserenergy from a Xenon Chloride excimer laser. The laser may comprisepulsed energy or substantially continuous energy, for example. Inembodiments, the laser energy delivered from the probe comprisesfemto-second or pico-second laser energy, for example.

The fiber-optic probe 23 may comprise an optical fiber or a plurality ofoptical fibers encapsulated by an encapsulating sheath. The diameter ofa single optical fiber should be sufficiently large to transmitsufficient light energy to effectively result in photoablation of targettissues. In some embodiments, the optical fiber diameter is in a rangefrom about 4-6 μm. A single optical fiber or a plurality of opticalfibers can be used in a bundle of a diameter ranging from about 100 μmto about 1000 μm, for example. The optical fiber core and cladding canbe encased within an outer metal sleeve, or shield. In some embodimentsthe sleeve is fashioned from stainless steel. In some embodiments, theouter diameter of sleeve is less than about 100 μm. In some embodiments,the diameter can be as small as 100 μm, as where smaller optical fibersare implemented with laser delivery systems. In some cases, the opticalfiber may have a diameter of about 200 μm and the fiber-optic probe 23may have a greater diameter such as 500 μm to encapsulate one or moreoptical fibers. In some embodiments, the sleeve can be flexible so thatit can be bent or angled.

FIGS. 4A and 4B show interior structures of the eye visible with anendoscope, such as an endoscope comprising a camera inserted to the eyeas described herein. Structures visible with the endoscope inserted intothe eye with an ab interno approach as described herein include theciliary body band 302 and the scleral spur 304. In some embodiments,Schwalbe's line 306 can be viewed with the camera inserted into the eye.In some embodiments, Schlemm's canal 308 can be seen in the cameraimage, depending on the intraocular pressure of the eye during surgery.In some embodiments, the intraocular pressure of the eye is sufficientlyhigh to limit blood from entering Schlemm's canal 308, and Schlemm'scanal may not be readily visible with the endoscope inserted into theeye as described herein, such as by an endoscope comprising a camerainserted into the eye as described herein. Also, in some embodiments,Schwalbe's line 306 may not be readily visible in the image provided bythe endoscope inserted into the eye, such as an endoscope comprising acamera inserted into the eye or an external sensor array as describedherein. The methods and apparatus disclosed herein can be well suitedfor identifying or estimated the locations structures of the eye thatmay not be readily visible from the endoscope inserted into the eye, soas to assist the surgeon with the placement of the treatment probe.

FIGS. 5A and 5B show images shown on a heads-up display from an in situcamera with markers presented on a display visible to a surgeon asdescribed herein, in accordance with some embodiments. Theprocessor-identified location of the ciliary body band 302 and theprocessor-determined location of Schlemm's canal 308 are shown withmarkers presented on the display visible to the surgeon. For example, acamera as described herein can be advanced with a treatment probe 500and capture real-time imaging data during a procedure. The real timeimaging data can be used by a processor to determine a location ofSchlemm's canal 308 in response to one or more of the ciliary body band302, iris root or the scleral spur 304. The processor can be configuredto display an estimated location of Schlemm's canal 308 with indiciasuch as markers, to assist the surgeon with placement of the probe onthe trabecular meshwork adjacent Schlemm's canal, so that the surgeoncan accurately place the probe on the trabecular meshwork overlyingSchlemm's canal 308. This approach can be helpful when Schlemm's canal308 is not readily visible in the camera image. Alternatively, or incombination, the processor can be configured to determine the locationof Schlemm's canal 308 from the location of Schlemm's canal 308 as shownin the image, for example when Schlemm's canal 308 comprises sufficientcontrast to be visible such as may occur with cataract surgery. AlthoughFIG. 5A shows markers on the real time images from the camera insertedinto the eye of the patient, in some embodiments the images are shown onthe heads up display without markers and the fixed orientation betweenthe camera and the probe allows the surgeon to determine the orientationof the probe in response to the images.

FIG. 5A illustrates a treatment probe 500 shown in the image, which maycomprise an optical fiber within a housing. In some embodiments, thecamera comprises an axis that is fixed rotationally in relation to anaxis of the probe. A camera may be affixed to, carried by, or bedisposed within a shared housing with the treatment probe 500, such thatthe camera captures images of the treatment probe 500 during aprocedure. The camera may aid a surgeon in delivering the treatmentprobe 500 to a target location, such as for performing a procedure,delivering and installing an implantable device, or for surveying areasof interest within a patient. As illustrated, the treatment probe 500 isplaced in proximity to Schlemm's canal 308 and the ciliary body band302. One or more of these anatomical features may be visible through thecamera system and are recognizable by a user. According to someembodiments, the camera is coupled to a controlling unit, as will bedescribed in further detail. The controlling unit may comprise aprocessor and instructions performable by the processor. In someembodiments, the instructions comprise one or more image analysisalgorithms that can detect anatomical features and landmarks. In someinstances, the controlling unit is able to identify anatomical featuresand augment the camera view by overlaying information, such as markers,for example a Schlemm's canal identifier 502, a ciliary body bandidentifier 504, or some other identifier or a combination ofidentifiers, onto the camera imaging data as described herein. Forinstance, the controlling unit, by executing one or more featurerecognition algorithms, may recognize the Schlemm's canal 308 and placea Schlemm's canal identifier 502. In some cases, the system mayrecognize Schlemm's canal 308 based upon a difference in contrast in theanalyzed image. For example, Schlemm's canal 308 may be identified basedupon a difference in contract of greater than 5%. Although Schlemm'scanal may comprise a generally annular structure in three-dimensionalspace, when viewed from within the anterior chamber, Schlemm's canal mayresemble a line which may be substantially straight or somewhat curveddepending on the field of view and the angle at which the cameraapproaches the site.

In some embodiments, the controlling unit augments the camera imagingdata by placing a Schlemm's canal identifier 502 that closely followsSchlemm's canal 308. The Schlemm's canal identifier 502 can resemble aline and can be updated to remain in an overlaid position with respectto the anatomical feature even as the camera moves. The augmented layeror at least some of the graphical elements of an augmented image can bemapped or matched to the optical image using object recognitiontechniques or pattern matching techniques, such as feature pointrecognition, edge detection, classifiers, spatial pyramid pooling,convolutional neural networks, or any of a number of suitable objectrecognition algorithms, or a combination of techniques. The Schlemm'scanal identifier 502 can be placed on the images substantially in realtime, for example with a latency of no more than five video frames, forexample with a latency within a range from one to four video frames.

Alternatively, or in combination, the controlling unit may recognize andidentify other anatomical features, such as the ciliary body band 302,as illustrated. Here, the controlling unit augments the camera imagedata by overlaying a ciliary body band identifier 504 to follow thegeneral shape of the ciliary body band 302. While the illustratedmarkers can be substantially straight lines, the markers may take othershapes and may be contoured to follow the anatomical contours at theimaged site. The markers may optionally denote the boundaries ofselected anatomical features, such as Schwalbe's line, scleral spur, orSchlemm's canal 308. For example, a plurality of dashed lines can beused to indicate the estimated anterior and posterior boundaries ofSchlemm's canal 308 with a central line extending along an estimatedcentral location of Schlemm's canal as shown in the camera image. Thisapproach can be helpful when Schlemm's canal is not readily visible inthe image viewed by the surgeon.

Other information, such as distances, arrows, directions, text, or otherinformation may be likewise used to augment the camera imaging data. Insome embodiments, the system may use identifiable features to locateother features. For example, the system may identify the scleral spur,and based upon the magnification, average distances and features sizes,the system may be able to identify the approximate location of Schlemm'scanal 308 based upon the recognized features, even if the imagerydoesn't readily show Schlemm's canal 308. For example, a processor maybe configured with instructions to determine a location of Schlemm'scanal 308 in response to identifying one or more of the ciliary bodyband 302 or the scleral spur and to display the location on a subsequentimage from the detector array of the camera

As shown in FIG. 5A, it is readily apparent that the camera is in arotated orientation with respect to Schlemm's canal 308. In someprocedures, it may be helpful to orient the treatment probe 500 withSchlemm's canal 308. By using the methods and apparatus disclosedherein, a user can quickly determine whether the treatment probe 500 isrotationally aligned with one or more structures of the eye such as oneor more of the iris root, the ciliary body band 302, the scleral spur,or Schlemm's canal 308. The markers, such as the Schlemm's canalidentifier 502 can provide further useful information for aligning thetreatment probe 500 with Schlemm's canal 308, which can be helpful whenSchlemm's canal 308 is not readily visible from the image of the cameraarray inserted into the eye for example.

As shown in FIG. 5B, once a user has rotated the treatment probe 500 andcamera, the camera image and associated data shows that Schlemm's canal308 and the associated Schlemm's canal identifier 502 are substantiallyhorizontal. In some cases, where the Schlemm's canal identifier 502, andas a result, Schlemm's canal 308 itself, is horizontal, then the user isassured that the treatment probe 500 is aligned with Schlemm's canal308. Of course, other marker information may be used or displayed toaugment the camera imaging data and may aid a user in approaching andorienting the treatment probe 500 with respect to any anatomical featureof interest.

With reference to FIGS. 6A and 6B, a treatment probe 500 is shown inproximity of Schlemm's canal 308 and the ciliary body band 302. Asillustrated, the treatment probe 500 carries a device, such as animplant 620, to the treatment site. In some embodiments, the implant 620comprises elongate implantation axis 622 sized and shaped to extendalong Schlemm's canal 308, and the implant 620 can be inserted intoSchlemm's canal 308 by aligning the elongate implantation axis 622 withan elongate axis of Schlemm's canal 308, which can be helpful forappropriate delivery of the implant 620. For example, the implant 620may comprise a sharp end sized and shaped to penetrate the trabecularmeshwork and slide along Schlemm's canal 308. The fixed orientation ofthe camera relative to one or more of the probe 500 or the implant 620can allow the user to align the implant with Schlemm's canal 308 withreference to structures shown in the image from the camera placed in theeye, such as with reference to one or more of the ciliary body band 302or the scleral spur, for example without computer generated markers andwhen Schlemm's canal 308 is not readily apparent in the image from thecamera placed in the eye. In some embodiments, the controlling unit mayaugment the camera images to show a Schlemm's canal identifier 502 toaid the user in locating Schlemm's canal 308 and also for determiningthe orientation of the treatment probe 500. As illustrated in FIG. 6A,the treatment probe 500, and thus the implant 620, is misaligned withrespect to Schlemm's canal 308 and should be reoriented in order toproperly deliver the implant.

As illustrated in FIG. 6B, the treatment probe 500 has been rotated tocoincide with the orientation of Schlemm's canal 308. This may be doneby viewing the camera image data to verify that Schlemm's canal 308 issubstantially horizontal. In the alternative, or in addition, theaugmented camera image data may show a Schlemm's canal identifier 502,which can be rotated by reorienting the treatment probe 500 and camerauntil the Schlemm's canal identifier 502 is substantially horizontal. Insome embodiments, the camera and treatment probe 500 are rotated untilthe elongate implantation axis 622 of the implant 620 is substantiallyparallel with the Schlemm's canal identifier 502, for example parallelto within about 10 degrees and in some embodiments parallel to withinabout 5 degrees. In some instances, the treatment probe 500 and cameraare rotated or repositioned until the elongate implantation axis 622 ofthe implant 620 is aligned with the Schlemm's canal identifier 502. Thiscan increase the accuracy of implant delivery and deployment, and can behelpful when Schlemm's canal 308 is not readily visible in the image,for example.

In some embodiments, additional identifiers or markers are overlaid toaugment the camera image data. Some of these may include identificationof other anatomical features, such as a ciliary body band identifier 504for example, distances between anatomical features, size of anatomicalfeatures, distance of the distal end of the probe from anatomicalfeatures, directional arrows other directions to aid in moving thetreatment probe 500, along with other useful information.

With reference to FIG. 7, a system 400 for aiding a physician to performa surgical procedure on an eye E, is illustrated in accordance with someembodiments. The surgical operation procedure may comprise inserting anelongate probe 23 from an opening into the eye across an anteriorchamber to a target tissue region comprising a trabecular meshwork and aSchlemm's canal. In some embodiments, the system 400 may comprise anoptical microscope 409 for the surgeon to view the eye during theprocedure in real-time. A camera input 401 receives a feed from thecamera 702 placed in the eye as input. The camera input 401 isoperatively coupled a processor 414 of the controlling unit 410. Theprocessor of the controlling unit 410 can be configured withinstructions to identify locations of structures of the eye and overlayindicia such as markers on the input camera images. In conjunction withthe optical microscope 409, a camera 702 placed in the eye may provide acamera input 401 to the controlling unit 410. In some embodiments, asecond camera 416 comprising a detector array is optically coupled tothe microscope 409 to receive optical images from the operatingmicroscope 409, and optically coupled to the processor 414 of thecontrol unit 410. The control unit 410 can receive the image data fromthe camera 416 and process the image data to provide visual image dataon the heads-up display 407 and overlay the visual image data on ananterior optical image of the operating microscope 409. The microscope409 may comprise a binocular surgical operating microscope, for example.The system 400 may comprise a camera 702 that is delivered in situ alongwith the treatment probe 23 to provide imaging of one or more targetlocations before, during, or after the procedure. The camera 702 of theprobe may comprise any suitable camera device, and in some cases, maycomprise a CCD or CMOS imaging sensor carried on or within an endoscopiccamera. Images captured by the camera may be processed by an imageprocessing apparatus 412 of the controlling unit 410 to generate aplurality of augmented images visualized by the physician in real time.

The augmented images can be shown on a display of the heads up display407, and combined with optical images from the microscope 409 with aninternal beam splitter 420 to form monocular or binocular images as isknown to one of ordinary skill in the art. As described herein, amicroscope view may comprise one or more of an optical microscope image,a camera image from a camera 702 placed in the eye, a microscope imageand an overlaid virtual image, or a microscope image in combination withimaging captured by the camera 702 with or without an overlaid virtualimage, for example. When a microscope view includes an overlaid image,the overlaid image can be registered with the microscope image usingelements which enable such alignment. Similarly, when the view includesimaging from the camera and an overlaid virtual image, the overlaidimage can be registered with the imaging from the camera using elementswhich enable such alignment.

The images can be provided to the surgeon in many ways. For example, thesurgeon can view the images with an augmented reality display such asglasses or goggles and view the surgical site through the operatingmicroscope 409. In some embodiments, the surgeon views the images with avirtual reality display. Alternatively or in combination, the eye can beviewed with an external monitor, and the images of the eye viewed withthe external monitor with markings placed thereon as described herein.The images viewed by the surgeon may comprise monocular images orstereoscopic images, for example.

According to some embodiments, a surgeon may first view a surgicalinstrument, such as a probe 23, in the microscope or a video image fromthe operating microscope. In some cases, the surgeon may alternatively,or additionally, view images captured by the camera 702 showing theprobe 23. According to some embodiments, a surgeon may view images fromthe microscope 409 and images captured from the camera 702 through theoculars of the microscope 409. Alternatively or in combination, thesurgeon may view an augmented image or view, where additionalinformation is overlaid on one or more of the optical microscope imageor the camera image. When there is an image captured by the cameraoverlaid on the image from the microscope image, the surgeon can viewboth the microscope image and concurrently the overlaid camera image.Furthermore, the image processing apparatus 412 can detect anatomicalfeatures of the eye as described herein, and overlay markers onto themicroscope image or the camera image to help guide a surgeon inidentifying and locating these features. The augmented images may bepresented to the physician through an eyepiece (or eyepieces) or ocularsof the microscope and/or a display of the microscope, and in someembodiments may be viewed on a monitor screen. This may be beneficial toallow a surgeon to maintain a stereoscopic view of an operative sitethrough the oculars of the microscope while simultaneously viewingsuperimposed or adjacent images or information concurrently eitherstereoscopically or monocularly, for example. Real-time images capturedby the camera 702 in situ and real time treatment information can besuperimposed to the live view of one or both oculars. In someembodiments, the apparatus and methods disclosed provide a real-timeview including real and augmented images from both outside and inside ofthe anterior chamber during these surgeries.

The optical microscope 409 may be operatively coupled to the endoscopeinserted into the eye in many ways. The optical microscope 409 maycomprise a binocular microscope such as a stereo-microscope comprisingimaging lens elements to image an object onto an eyepiece(s) comprisingan ocular 408. The endoscope placed in the eye is configured to captureoptical images of the eye, and may comprise any endoscope as describedherein. The optical images may be transmitted to the controlling unit410 for processing. The endoscope may comprise optical elements (e.g.,lens, mirrors, filters, prisms, etc. to form an image on a sensor arrayas described herein. The sensor array may capture color images,greyscale images and the like, and may be introduced with the treatmentprobe 23 and moved with the treatment probe 23, or the treatment probe23 may move independently of the endoscope while maintaining rotationalalignment with the treatment probe 23. In some instances, the treatmentprobe 23 and the endoscope as described herein move together duringinsertion to a location of interest, and then the treatment probe 23 andthe endoscope as described herein can move independently of the otherwhile maintaining rotational alignment. The probe 23 may be the sametreatment probe 500 as described herein with various embodiments. Theprobe 23 may be configured with a handpiece 704 to allow insertion,manipulation, or withdrawal of the probe 23, such as by a user, anactuator, a robotic arm, or otherwise.

The endoscopic images may be acquired at an appropriate image frameresolution and/or an appropriate image frame rate, and the resolutionmay comprise resolution of the camera inserted into the eye or opticalresolution of an external sensor array optically coupled to a lens nearthe end of the endoscope. The image frame resolution may be defined bythe number of pixels in a frame. The image resolution of the detector ofthe camera place in the eye may comprise any of the followingresolutions: 160×120 pixels, 249×250, 250×250, 320×240 pixels, 420×352pixels, 480×320 pixels, 720×480 pixels, 1280×720 pixels, 1440×1080pixels, 1920×1080 pixels, 2048×1080 pixels, 3840×2160 pixels, 4096×2160pixels, 7680×4320 pixels, or 15360×8640 pixels. The resolution of thearray detector, e.g. the detector placed in the eye or the externaldetector, may comprise a resolution within a range defined by any two ofthe preceding pixel resolutions, for example within a range from 160×120pixels to 250×250 pixels, e.g. 249×250 pixels. The imaging device orcamera may have pixel size smaller than 1 micron, 2 microns, 3 microns,5 microns, 10 microns, 20 microns and the like. The camera inserted intothe eye may have a footprint on the order of 2 mm×2 mm, or 1 mm×1 mm,0.8 mm×0.8 mm, or smaller, which is suitable for insertion alongside atreatment probe 500. The external sensor array may comprise similardimensions.

The captured images from the sensor array, e.g. the camera inserted intothe eye or the external sensor array, may comprise a sequence of imageframes captured at a specific capture rate. In some embodiments, thesequence of images may be captured at standard video frame rates such asabout 24p, 25p, 30p, 43p, 48p, 50p, 60p, 62p, 72p, 90p, 100p, 120p,300p, 50i or 60i, or within a range defined by any two of the precedingvalues. In some embodiments, the sequence of images may be captured at arate less than or equal to about one image every 0.0001 seconds, 0.0002seconds, 0.0005 seconds, 0.001 seconds, 0.002 seconds, 0.005 seconds,0.01 seconds, 0.02 seconds, 0.05 seconds, or 0.1 seconds. In some cases,the capture rate may change depending on user input and/or externalconditions under the guidance of the control unit 410 (e.g. illuminationbrightness).

The images captured by the sensor array, e.g. the camera inserted intothe eye or the external sensor array, may be captured in real time, suchthat images are produced with reduced latency, that is, with negligibledelay between the acquisition of data and the rendering of the image.Real time imaging allows a surgeon the perception of smooth motion flowthat is consistent with the surgeon's tactile movement of the surgicalinstruments (e.g. the elongate probe and the probe tip) during surgery.Real time imaging may include producing images at rates of about orfaster than 30 frames per second (fps) to mimic natural vision withcontinuity of motion, and at twice that rate to avoid flicker(perception of variation in intensity). In some embodiments, the latencymay comprise a time interval from capturing the images from the camerauntil information is shown to the user, which may be no more than about100 ms, for example 50 ms or less. In some embodiments, the latencycomprises no more than one or two frames of the image shown on thedisplay.

In some embodiments, the optical microscope 409 may be coupled to anelectronic display device 407. The electronic display 407 may comprise aheads-up display device (HUD). The HUD may or may not be a component ofthe microscope system 409. The HUD may be optically coupled into thefield-of-view (POV) of one or both of the oculars 408. The displaydevice may be configured to project augmented images from input 401generated by the controlling unit 410 to a user or surgeon. The displaydevice 407 may alternatively or additionally be configured to projectimages captured by the camera to a user or surgeon. The display devicemay be coupled to the microscope via one or more optical elements suchas beam-splitter or mirror 420 such that a physician looking into theeyepieces 408 can perceive in addition to the real image, cameraimaging, augmented images, or any combination represented and presentedby the display device 407. The display device may be visible through asingle ocular to the surgeon or user. Alternatively, the HUD may bevisible through both eyepieces 408 and visible to the surgeon as astereoscopic binocular image combined with the optical image formed withcomponents of the microscope, for example.

The display device of heads-up display 407 is in communication with thecontrolling unit 410. The display device may provide augmented imagesproduced by the controlling unit 410 in real-time to a user. Asdescribed herein, real time imaging may comprise capturing the imageswith no substantial latency and allows a surgeon the perception ofsmooth motion flow that is consistent with the surgeon's tactilemovement of the surgical instruments during surgery. In some cases, thedisplay device 407 may receive one or more control signals from thecontrolling unit 410 for adjusting one or more parameters of the displaysuch as brightness, magnification, alignment and the like. The imageviewed by a surgeon or user through the oculars or eyepieces 408 may bea direct optical view of the eye, images displayed on the display 407 ora combination of both. Therefore, adjusting a brightness of the imageson the HUD may affect the view of the surgeon through the oculars. Forinstance, processed information and markers shown on the display 407 canbe balanced with the microscope view of the object. The processor mayprocess the camera image data, such as to increase contrast of the imagedata so the visible features are more readily detectable oridentifiable.

The heads up display 407 may be, for example, a liquid crystal display(LCD), a LED display, an organic light emitting diode (OLED), a scanninglaser display, a CRT, or the like as is known to one of ordinary skillin the art.

Alternatively or in combination, the display 407 may comprise anexternal display. For example, the display 407 may not be perceivablethrough the oculars in some embodiments. The display 407 may comprise amonitor located in proximity to the optical microscope 409. The display407 may comprise a display screen, for example. The display 407 maycomprise a light-emitting diode (LED) screen, OLED screen, liquidcrystal display (LCD) screen, plasma screen, or any other type ofscreen. The display device 407 may or may not comprise a touchscreen. Asurgeon may view real-time optical images of the surgical site andimaging provided by the in-situ camera 702 simultaneously from thedisplay 407.

The resolution of the endoscope can be configured in many ways withappropriate optics and sensor resolution to image the target tissue atan appropriate resolution. The sensor array of the endoscopic camera orthe external sensor array may comprise a suitable resolution for viewingtissue structures of the eye as described herein and may comprise aresolution within a range from less than 1 to 10 microns, for examplewithin a range from about 3 to 6 microns, for example. In someembodiments, the sensor array such as the camera sensor array or theexternal sensor array, comprises a spatial resolution, e.g. imagespatial resolution, within a range from about 10 μm to about 80 μm fortissue contacting the inclined distal end of the probe (or contactingthe implant). In some embodiments, the resolution is within a range fromabout 20 μm to about 40 μm.

In some embodiments, lights that are present for the operatingmicroscope provide sufficient illumination. In some embodiments, thecamera placed in the eye may optionally comprise a light source suitablefor producing images having suitable brightness and focus. In someembodiments, the camera placed in the eye may comprise a light-emittingdiode (LED), an optical fiber for illumination, or MicroLED. In someembodiments, one or more color filters can be applied to the imagingcaptured by the camera in order to help isolate, locate, or otherwiseidentify tissue structures of interest. The camera placed in the eye maybe at least partially controlled by the controlling unit 410. Control ofthe camera 702 by the controlling unit may include, for example,activation of the sensor array, parameters set-up, focus, brightness,contrast, application of one or more filters, or customizable controlparameters.

The camera placed in the eye may comprise a miniature image sensorhaving a high signal to noise ratio. The camera may comprise a lens anda sensor array. In some embodiments, one or more lenses of the cameracomprises borofloat glass, for example. The sensor array may have anysuitable number pixels arranged in a row and column array. In someembodiments, the pixel array comprises 249×250 pixels, which maycomprise rolling shutter pixels, for example. In some embodiments, thepixels have a pitch of 3 μm, which results in an optical area of 1.06 mmdiameter, for example.

The system 400 may further comprise a user interface 413. The userinterface 413 may be configured to receive user input and provide outputinformation to a user. The user input may be related to control of asurgical tool such as the probe 23. The user interface 413 may receivean input command related to the operation of the optical microscope(e.g., microscope settings, camera acquisition, etc.). The userinterface 413 may receive an indication related to various operations orsettings about the camera. For instance, the user input may include aselection of a target location, a selection of a treatment referencemarker, displaying settings of an augmented image, customizable displaypreferences and the like. The user interface 413 may include a screensuch as a touch screen and any other user interactive external devicesuch as handheld controller, mouse, joystick, keyboard, trackball,touchpad, button, verbal commands, gesture-recognition, attitude sensor,thermal sensor, touch-capacitive sensors, foot switch, or any otherdevice.

In some embodiments, the camera placed in the eye is used for guidingthe probe 23 and visualization of the target site. In some embodiments,the camera 702 can be configured to view tissue and the probe tip. Insome embodiments, the lens of the camera is located at a distance ofabout 10 mm from the probe tip, for example at least about 6 mm from theprobe tip. These distances allow the probe tip to be seen on the cameraimage to target Schlemm's canal.

The controlling unit 410 may be configured to generate an augmentedlayer comprising the augmented information. The augmented layer may be asubstantially transparent image layer comprising one or more graphicalelements. The terms “graphical element” and “graphical visual element”may be used interchangeably throughout this application. The augmentedlayer may be superposed onto the optical view of the microscope, opticalimages or video stream, and/or displayed on the display device. In someembodiments, the augmented layer is superimposed onto the optical viewof the microscope, such that the transparency of the augmented layerallows the optical image to be viewed by a user with graphical elementsoverlaid on top of it. In some embodiments, the augmented layer maycomprise real time camera images or other information obtained by one ormore of the camera 702 placed in the eye or camera 416.

As described herein, the fusing of the optical microscopic image data,the camera image data, the augmented information, or any combination,may comprise incorporating the augmented information into the opticalmicroscopic image or the camera image data, or both. The augmented imagedata may comprise one or more graphical elements associated with thedepth information, target location, orientation information, tissueidentification information, or various other supplemental information.The graphical elements may be overlaid onto the optical microscopicimage and/or the camera image with a beam splitter 708, for example. Agraphical element can be directly overlaid onto an image of any objectvisible in the optical microscopic image. A graphical element may alsoinclude any shape, boundary, or contour surrounding an image of anyobject in the optical microscopic image. The object may be, for example,an instrument inserted into the eye (e.g., probe), a portion of theprobe, target tissues as described herein, and the like.

In some embodiments, the graphical elements may be configured todynamically change as a position or an orientation of the probe orinstrument changes relative to a target location. For example, agraphical element may indicate a location of a distal end of the probeshown in the optical image, or relative location or spacing betweentissues such as inner wall of SC, TM and the like. The graphicalelements may be configured to dynamically show the change in spacingbetween the tissue walls or distance between the tip and a targetlocation substantially in or near real-time on the optical image, as therelative distance between the probe tip and a target location changes,and/or when the probe tip compresses on tissue (e.g., the probe tipcontacting the surface of trabecular meshwork).

In some embodiments, the augmented information may comprise anorientation of the probe relative to the target location. The graphicalelements may indicate the orientation of the probe relative to thetarget location. The graphical elements may be configured to dynamicallyshow the orientation of the probe relative to the target locationsubstantially in or near real-time on the optical image, as theorientation between the probe and the target location changes. In someinstances, a graphical element may indicate an orientation or axiallocation of the elongated probe. To indicate orientation (e.g.,direction), the graphical element may be provided in the form of anarrow, or a line. The graphical element may be configured to changedynamically based on movement/advancing of the probe.

The augmented layer or at least some of the graphical elements can bemapped or matched to the optical image using object recognitiontechniques or pattern matching techniques, such as feature pointrecognition, edge detection, classifiers, spatial pyramid pooling,convolutional neural networks, or any of a number of suitable objectrecognition algorithms, or a combination of techniques. A feature pointcan be a portion of an image (e.g., scleral landmarks, collector channelpatterns, iris landmarks, etc.) that is uniquely distinguishable fromthe remaining portions of the image and/or other feature points in theimage. A feature point may be detected in portions of an image that arerelatively stable under perturbations (e.g., when varying illuminationand brightness of an image).

With reference to FIG. 8, an exemplary augmented image providing anaugmented view 600 is shown. As described herein, the augmented image600 may be viewed binocularly by a user or surgeon through oculars ofthe microscope, and may be displayed on a heads-up display, an externaldisplay device, or a display coupled to a user interface. The augmentedimage or view may comprise an optical image 505 or an optical path viewthrough the oculars of an optical microscope. The optical image 505 maycomprise a top-down view of the eye. The optical image 505 or opticalview may show anterior of an eye. The optical image 505 or optical viewmay further show an elongated probe 23. The augmented image or view 600may comprise a plurality of graphical visual elements and one or morecamera images 802 from the camera adjacent to or overlaid over theoptical image 505, for example by optically coupling the display to theoptical path of the microscope, such as with a beam splitter. Theplurality of graphical visual elements may comprise different shapesand/or colors corresponding to different objects such that differentobjects shown in the optical image 505 can be easily distinguished fromone another. For example, the camera image may be overlaid with anidentification and location of Schlemm's Canal, such as a Schlemm'scanal identifier 502, which may also provide an indication of therotational orientation of the probe relative to the anatomical features.

The plurality of graphical visual elements may comprise one or moretreatment reference markers 601, 602, 603 mapped to the one or moretarget locations. As discussed elsewhere herein, treatment referencemarkers 601, 602, 603 may correspond to target locations which are notoptically visible to the surgeon in the optical image from the operatingmicroscope. According to some embodiments, target locations may belocated ab interno, and treatment of the target locations may involve anab interno approach. In some cases, the one or more target locations maybe determined or identified based on preoperative or intraoperativeimages. As discussed elsewhere herein, preoperative and/orintraoperative images may be obtained using either ab interno approachesand/or ab externo approaches, for example. The treatment referencemarkers 601, 602, 603 may be registered with one or more camera images802. In some embodiments, a view from a microscope, such as an operatingmicroscope, can view the probe. Additionally, the view from the probecan be superimposed on the microscope view, and the augmented view mayshow the end of the probe and the two images can be aligned orregistered with one another. This provides the surgeon additional visualinformation about the position, location, orientation, and direction ofthe probe relative to anatomical markers. In some cases, the images fromthe microscope and the probe are aligned with one another enablingvisible anatomical markers from both image sources to be aligned in anoverlaid image, or in a picture-in-picture image. In some instances, theimages from the microscope and the probe are provided to a surgeon inreal-time, or in such a way that the images provide real-timeinformation to the surgeon during a procedure.

According to some embodiments, a treatment reference marker or targetlocation can be selected based on a location in the target tissue regionthat would provide a significant increase in outflow following theformation of a channel therethrough (e.g. channel passing through thetrabecular meshwork, the juxtacanalicular trabecular meshwork, and theinner wall of Schlemm's canal, thus providing fluid communicationbetween the anterior chamber and Schlemm's canal). Such a selection canbe based on an identification of certain regions in collector channelnetworks or fields that are denser, or that contain larger vessels, or alarger distribution of vessels, or that are less obstructed, or thatcorrespond to circumferential flow areas provided by Schlemm's canal.During real time imaging, the one or more treatment reference markers601, 602, 603 may be superimposed over the microscope imaging, thecamera imaging, or both, to the target locations by detecting a patternof the target location identified from the preoperative imaging or realtime camera imaging. In some cases, a user or surgeon may be prompted toselect a target location(s) or treatment reference marker(s) through theuser interface 413. In some cases, a user or surgeon may be prompted torank or order selected target locations for treatment. Hence, the useror surgeon can specify a desired sequence in which the target locationswill be treated during the surgical procedure. For example, the user orsurgeon can specify that treatment reference marker 601 corresponds to atarget location that will be treated first, that treatment referencemarker 602 corresponds to a target location that will be treated second,and that treatment reference marker 603 corresponds to a target locationthat will be treated third.

As discussed elsewhere herein, treatment reference markers can beselected based on locations (e.g. locations in a target tissue region)that have been determined to correspond to bigger collector channels,more dense collector channel networks or fields, and/or and greateroutflow. In some cases, the treatment reference markers can be selectedin an automated fashion. In some cases, the treatment reference markerscan be selected manually. Systems can be configured to guide the surgeonto direct the laser fiber to each of the selected treatment referencemarkers, sequentially. In some cases, a plurality of treatment referencemarkers may be shown simultaneously such as in the beginning of aprocedure for a user to select a target location. In some cases, theplurality of treatment reference markers may be shown sequentially asthe surgical operation progresses.

The plurality of graphical visual elements may also comprise a probeline 604 coaxial with the elongate probe 23. The probe line 604 shows anorientation of the probe in relation to the one or more targetlocations. The plurality of graphical visual elements may also comprisea distal tip marker 605 overlapping with the distal end of the elongatedprobe. Both of the probe line and the distal tip marker may dynamicallychange locations with respect to the actual positions and orientation ofthe elongate probe shown in the optical image or view 505, as the probeis moved within the anterior chamber of the eye. Hence, for example, asurgeon can use microscope to see the probe 23 as it enters the anteriorchamber and can watch the probe as it moves relative to the eye. Adetection mechanism can detect the probe 23, and an automated system orprocessor can generate the probe line 604 in response to the detection.Similarly, the automated system or processor can generate the guidancearrow 612.

The plurality of graphical visual elements may further comprise one ormore guidance arrows or markers 612 extending from the distal tip marker605 towards the one or more treatment reference markers (e.g., marker601). The one or more guidance arrows 612 may be configured to guide thephysician in aligning the distal end of the elongate probe to pointtowards the one or more target locations during the procedure or guidethe physician in advancing the elongate probe towards the one or moretarget locations during the procedure. As discussed elsewhere herein,the one or more target locations may not be optically visible to thesurgeon in the microscope view 505, and the camera imaging may besuperimposed to allow the surgeon to see real-time imaging of the distaltip of the probe.

For example, upon a selection of a target location, a guidance arrow 612may be generated pointing from the distal end of the probe (or thedistal tip marker 605) to the selected target location (or thecorresponding treatment reference marker) such that the physician mayadvance the probe parallel or coaxial to the guidance arrow. The one ormore guidance arrows 612 may point radially from within the anteriorchamber in different directions toward the target tissue regioncomprising the trabecular meshwork and the Schlemm's canal. As discussedelsewhere herein, the height of Schlemm' s canal may be about half theheight of the trabecular meshwork. In some cases, the one or moreguidance arrows may automatically appear when the distal end of theprobe is located at a predetermined distance away from the targetlocation, for example when the distal end of the probe is located about6 mm or less from the target location. Alternatively, the one or moreguidance arrows may appear in response to a user input indicating atarget location selected from the plurality of target locations.

A specific anatomical identifier may be superimposed over the microscopeimaging or the camera imaging and may aid the surgeon in location theposition and orientation of anatomical features. For example, aSchlemm's Canal Identifier 502 may be provided as an overlay on thecamera imaging to show a surgeon the location and orientation ofSchlemm's canal. As illustrated, the camera (and probe) are rotatedrelative to Schlemm's canal. Based upon this real-time imaging, thesurgeon can reorient the probe until the Schlemm's Canal Identifier 502is substantially horizontal and the probe is then aligned with Schlemm'scanal. Other indicia, such as a horizontal marker can be overlaid so thesurgeon rotate the probe until the Schlemm's Canal Identifier becomesubstantially parallel with the horizontal marker. In some embodiments,the image from the camera placed in the eye is shown on the heads updisplay without markers, so that the surgeon can manipulate the probewith rotation to align the probe with structures visible in the imagesuch as one or more of the ciliary body band 302, the iris root 16, orthe trabecular meshwork 9, for example, which can be helpful torotationally align the probe with Schlemm's canal for implantation orlaser treatment with an inclined optical fiber as described herein.

In some cases, real time or substantially real-time camera images may bedisplayed overlying the microscope image in a picture-within-pictureformat. Alternatively, or in combination, information derived from thecamera image may be overlaid on the microscope image. In someembodiments, when the distal end of the probe is within a predetermineddistance to the selected target location, a marker or indicia may beoverlaid on the microscope and/or camera imaging.

Advantageously, embodiments of the present invention provide systems andmethods that enable the surgeon to effectively and accurately move andposition a surgical instrument or probe, such as an excimer lasertrabeculotomy (ELT) device, throughout various desired or targetlocations in the peripheral anterior chamber by viewing real timeimaging from an in situ camera delivered with the treatment probe 500.

Embodiments of the present disclosure also enable the surgeon toeffectively and accurately move and position a surgical instrument orprobe, such as a laser trabeculotomy (“ELT”) device, by viewingreal-time imaging data from a camera located in close proximity to theprobe as described herein.

FIGS. 9A and 9B show examples of implants 620 and instruments that canbe used to place implants 620 in the trabecular meshwork, in accordancewith some embodiments. The implanted device 1220 a may comprise asubstantially elongated shape, and may any suitable implant and may bethe same implant 620 as described elsewhere herein.

As illustrated in the anterior view of an eye depicted in FIG. 9A,augmented information may be overlaid onto the optical view or image 505of the eye and the instrument in a similar as described elsewhereherein. For instance, one or more treatment reference markers 601 and anarrow or probe line 604 co-axial to the instrument 24 may besuperimposed to the optical image 505. The images shown in FIG. 9A canbe combined with an image from the camera placed on the eye and providedon the heads up display as described herein.

In some embodiments, the implant 620 comprises an elongate structureextending along an elongate axis sized and shaped for placement bysliding the implant along Schlemm's canal, for example with a sharp end902 as described herein. The detector placed in the eye may comprise anaxis extending along rows or columns of the detector, in which the axisof the detector is aligned with the elongate axis of the implant 620 towithin about five degrees, for example to within about 3 degrees, forexample to within about two degrees. For example, the axis of the camera702 may comprise a row of detectors of the array, and the row ofdetectors can be aligned with the elongate axis of the implant so thatthe elongate axis of the implant. Alternatively, the columns of thedetector array may extend along the elongate axis 904 of the implant.This can allow the user to tell when the elongate axis 904 of theimplant is aligned with Schlemm's canal, for example.

A guidance arrow 612 may be displayed to guide the advancing directionand orientation of the instrument 24. In some cases, the camera 702 maybe co-axial or enclosed in a housing of the instrument 24 to provide arelative position of the distal end of the instrument with respect totreatment location. In some embodiments, the camera 702 will be carriedby the instrument.

In some embodiments, an elongate probe 24 may comprise one or moreimplants 1220 a, such as an implant, loaded thereon, and the implants1220 a may be implanted in the trabecular meshwork 9 and configured toconnect the anterior chamber to the Schlemm's canal and create apermanent opening into Schlemm's canal. Embodiments of the methods andapparatus described herein can be configured to aid a physician inadvancing and implanting the one or more implants 1220 a at targetlocations with aid of the graphical visual elements (e.g. treatmentreference markers and arrows) registered with a real microscope image ofthe eye or a real camera image of the eye, or a combination of images.While the implant 1220 a can be any suitable implant, in some cases, theimplant will be an implant and that term will be used herein to refer toan implant delivered by the treatment probe 24. For example, thedisclosed system may be configured to aid the physician in advancing andsliding an implant 1220 a sideways into Schlemm's canal and positioningthe implant permanently in Schlemm's canal with aid of the graphicalvisual elements (e.g. treatment reference marker 601, probe line 604,Schlemm's canal identifier, ciliary body band identifier, and/orguidance arrow 612) registered with the microscope image.

In some embodiments, one or more of the inserter or the implantcomprises an engagement structure to align the elongate structure of theimplant with the axis of the camera. As shown in FIG. 9A-1 a proximalportion of the implant may comprise a channel such as a slot or groove906 sized and shaped to receive a protrusion of the inserter so as tofix the angle of elongate axis of the implant with the axis of thecamera.

In some cases, the system may be configured to aid the physician inadvancing a plurality of implants along an elongate axis 604 of theelongate probe, injecting the plurality of implants into Schlemm'scanal, and positioning the plurality of implants permanently inSchlemm's canal, with aid of the graphical visual elements registeredwith the microscope image. For example, as depicted in FIG. 9B, Panel(1), an elongate probe 1210 b includes a housing 1212 b and an insertionmechanism 1214 b. The probe 1210 b may be the same as other embodimentsdescribed herein and may be used with the systems and methods describedherein. The insertion mechanism 1214 b may comprise a stylet and aninserter housing configured to be inserted into a patient's eye. Thestylet may comprise a distal tip which is visible with the camerainserted into the eye to facilitate placement. The optical axis of thecamera as described herein may extend substantially parallel to anelongate axis of the stylet, e.g. within about 2 degrees, or be inclinedin relation to the stylet, such that the tip of the stylet appearsapproximately centered in the image from the camera place in the eye,e.g. appears within about 20 pixels of the center of the image fromcamera placed in the eye as described herein. The inserter housing 1215may comprise a treatment probe 500 and a camera, as described herein. Asdepicted in Panel (2), the insertion mechanism 1214 b can be loaded withan implant 1220 b, and the implant 1220 b can include a head 1222 b, athorax 1224 b, a flange 1226 b, and an outflow orifice 1228 b. A stylettip 1217 on the insertion mechanism 1214 b aids in aligning andinserting the implant. FIG. 9B, Panel (3) depicts two implants 1220 bwhich have been implanted into the trabecular meshwork 9, as viewed fromthe anterior chamber. As shown here, the flange 1226 b of each implant1220 b includes an inlet orifice 1227 b, which is in fluid communicationwith one or more outflow orifices (not shown).

These implants can be placed in the eye with a heads up display andcamera placed in the eye as shown and described with reference to FIG.9A For example, camera guidance embodiments as discussed with referenceto FIGS. 6A and 6B can be used to help guide the surgeon to implant animplant at a target location in the trabecular meshwork corresponding toSchlemm's canal. In some cases, the target location can correspond tothe location of a collector channel or be based on the distribution ordensity of multiple collector channels. With returning reference to FIG.9B, as depicted in Panel (4), when an implant 1220 b is implanted in theeye, the flange 1226 b resides in the anterior chamber 7, the thorax(not visible) resides in the trabecular meshwork 9, and the head 1222 bresides in Schlemm's canal. Because the inlet orifice is in fluidcommunication with the outflow orifices, aqueous humor can flow from theanterior chamber into Schlemm's canal.

The system can also be configured to aid the physician in positioning animplant in an anterior chamber angle 28 with aid of the graphical visualelements registered with the microscope image or the camera image, orboth. The in-situ camera imaging guidance embodiments as disclosedherein are well suited for assisting the surgeon in delivering theimplant (while loaded on the elongate probe) to the anterior chamberangle. For example, camera guidance embodiments as discussed withreference to FIGS. 6A and 6B can be used to help guide the surgeon toplace an implant at a target location in the anterior chamber angle.

With reference to FIG. 10 an example treatment probe 500 and camera 1002are illustrated in accordance with some embodiments. The camera 1002 iscontained within a camera housing 1004 and comprises a detector array1006 and a lens 1008. As described elsewhere herein, the detector array1006 may comprise an array with any suitable resolution for examplewithin a range from 200×200 to 300×300 pixels, for example.

A fastener 1010 such as a clip has a fastener length 1011 and may beused to couple the camera housing 1004 to an optical fiber housing 1012.The optical fiber housing 1012 may comprise an optical fiber 1014configured to deliver light energy to a treatment site. The opticalfiber housing 1012 and the optical fiber 1014 may comprise a treatmentprobe 500 and the camera 1002 and camera housing 1004 may comprise animaging probe 1000. The optical fiber housing 1012 may be configuredwith one or more structures that cooperate with the fastener 1010 tosecure the optical fiber housing 1012 and the camera housing 1004 in afixed relative rotational orientation. In other words, the fastener 1010may secure the camera housing 1004 and the optical fiber housing 1012together such that neither the camera housing 1004 or the optical fiberhousing 1012 can rotate substantially about their longitudinal axesindependently of the other, for example no more than about 2 degrees.The fastener 1010 may be permanently affixed to either the camerahousing 1004 or the optical fiber housing 1012 and selectively engagethe other. Alternatively, the fastener 1010 may comprise a separate partconfigured to couple to the treatment probe 500 and the imaging probe1000.

The distal end of the treatment probe 500 may be formed with an inclinedsurface 1020 having an angle α relative to the longitudinal axis of thetreatment probe 500. In some embodiments, the distal end of thetreatment probe 500 or the distal end of the optical fiber 1014, orboth, are inclined at an angle α of about 45 degrees to about 65 degreesand optionally at an angle within a range from about 50 degrees to about60 degrees. In some embodiments the angle α of the distal end of thetreatment probe 500 is the same as the angle of the distal end of theoptical fiber 1014. In some embodiments, the angle α of the distal endof the treatment probe 500 is within 10 or fewer degrees of the angle ofthe distal end of the optical fiber 1014.

While the illustrated embodiment shows a single optical fiber 1014, itshould be appreciated that a bundle of optical fibers could be used withthe disclosed systems and methods. In some examples, the treatment probe500 comprises a bundle of optical fibers that each have a distal end ator near the angle of the distal end of the treatment probe 500.

In some embodiments, the camera housing 1004 can translate along itslongitudinal axis in a direction N independently of the optical fiberhousing. In some cases, the translation distance of the camera housing1004 is fixed, such that there are limits to the translation distance ofthe camera housing 1004 relative to the optical fiber housing 1012. Insome embodiments, the distal end of the probe extends beyond the lens1008 of the 1002 camera by a distance A within a range from about 2 mmto about 10 mm, or within a range from about 2.5 mm to about 5 mm. Inembodiments, in which the camera housing 1004 can translateindependently of the optical fiber housing 1012, the translationdistance may be bounded by these dimensions, such that the lens 1008 ofthe camera 1002 can be moved to about 2 mm to about 10 mm from thedistal end of the optical fiber housing 1012.

Similarly, the detector array 1006 may be positioned a distance B fromthe distal end of the treatment probe 500. The distance B may be withinthe range of from about 2.5 mm to about 10.5 mm and optionally withinthe range of from about 3 mm to about 6 mm. The camera housing 1004 maybe limited in its translational range of motion relative to the opticalfiber housing 1012 such that the detector array 1006 may be limitedwithin the range of from about 2.5 mm to about 10.5 mm at the limits ofits longitudinal travel. The travel limits may be provided by anysuitable structure or mechanism, such as slots, grooves, protrusions,bosses, stops, and the like.

The treatment probe 500 may be translated in a direction M, and thecamera housing 1004 may be secured to the treatment probe 500 such thatthe camera housing 1004 is translated along with the treatment probe500. In some embodiments, the camera housing 1004 may have a rigidattachment to the optical fiber housing 1012 and be selectively releasedto provide a degree of freedom for translating along its longitudinalaxis within translational limits, as described herein.

The camera 1002 of the imaging probe 1000 may comprise an optical axis1022. The optical axis 1022 may extend approximately parallel to anelongate axis of the optical fiber 1014, for example parallel to withinabout 5 degrees. Although the optical axis 1022 can be inclined relativeto the elongate axis of the treatment probe 500 as described herein. Insome embodiments, the optical fiber 1014 comprises an inclined distalend 1020. The rows and columns of the detector array 1006 can be alignedwith the inclined distal end of the probe, so that the images from thecamera placed in the eye are aligned with the inclined distal end 1020of the probe. The inclined distal end 1020 may comprise a substantiallyflat surface that defines a surface normal vector 1024. The camera 1002can be positioned in relation to the surface normal vector 1024 in manyways. In some embodiments the surface normal vector 1024 and the opticalaxis 1022 extend along a common plane. In some embodiments, the inclineddistal end 1020 faces away from the optical axis 1022, for example withthe surface normal vector 1024 directed away from the optical axis 1022.In alternative embodiments, the inclined distal end 1020 faces towardthe optical axis 1022, for example with the surface normal vector 1024directed toward the optical axis.

In some embodiments, the rows and columns of the detector array 1006 arealigned with the inclined distal end 1020 of the probe 500, such thatthe columns of the array extend in a direction corresponding to thecomponent of the surface normal vector 1024 extending away from theelongate axis of the optical fiber. Alternatively the rows and columnsof the detector array 1006 can be rotated relative to the inclineddistal end 1020 of the fiber, and a processor used to rotate the imageshown to the surgeon in order to align the image of the eye from thecamera placed in the eye with the inclined distal end 1020 of the probe.

FIG. 11 is a cross-sectional schematic view of the probe 500 of FIG. 10taken along the line A-A. The probe 500 may have a camera 1002comprising a camera housing 1004 and a lens 1008. An optical fiberhousing 1012 may comprise one or more optical fibers 1014. The opticalfiber housing 1012 may be affixed to the camera housing 1004 to preventindependent rotation of the camera housing 1004 or the optical fiberhousing 1012.

According to some embodiments, a fastener 1010 may affix the opticalfiber housing 1012 to the camera housing 1001. The fastener 1010 maycomprise a clip which may be secured in a longitudinal groove of theoptical fiber housing 1012. In some embodiments, the clip is affixed tothe camera housing 1004 and comprises an engagement structure 1102 suchas, for example, a flat engaging surface, a slot, a key, a groove, anaperture, a protrusion, or other suitable structure. In someembodiments, the clip couples the optical fiber housing 1012 to thecamera housing 1004 with a fixed angular orientation.

In some embodiments, the camera housing 1004 or the optical fiberhousing 1012, or both, have flat engaging surfaces to provide intimatesurface contact between the camera housing 1004 and the optical fiberhousing 1012, and to orient the optical fiber housing 1012 for receivingthe fastener.

The camera housing 1004 has a maximum dimension D within the range ofabout 0.8 mm to about 1.2 mm. The optical fiber housing 1012 has amaximum cross-sectional dimension E within the range of from about 300μm to about 600 μm. While the camera housing 1004 and the optical fiberhousing 1012 are represented schematically as having a generallycylindrical cross section, the respective housings may have any suitablecross-sectional shape, such as ovoid, hexagonal, octagonal, circular, orany suitable shape.

In some embodiments, the fastener 1010 may comprise a clip or anaperture to engage one or more of the camera housing 1004, the inserterhousing 1215, or the optical fiber housing 1012 and optionally the clipcomprises the engagement structure 1102 sized and shaped to receive thecamera housing 1004, the inserter housing 1215, the optical fiberhousing 1012, or a combination.

The fastener may allow the camera housing 1004 to slide in relation tothe inserter housing 1215 or the optical fiber housing 1012 while therotational orientation of the camera 1002 to the inserter housing 1215or the optical fiber housing 1012 remains fixed.

The imaging probe 1000 comprising the camera 1002 may be fastened to thetreatment probe 500 with the fastener, such that the rotationalorientation of the camera 1002 relative to the rotational orientation ofthe instrument is fixed, that is, the camera 1002 cannot substantiallyrotate independently of the treatment probe 500, e.g. more than fivedegrees, for example no more than two degrees, e.g. no more than onedegree. In some embodiments, the rotation orientation is fixed by use ofcooperating structures that reduces the likelihood of relative rotationbetween the camera 1002 and the instrument. In some embodiments, a clipsecures the camera 1002 or the camera housing 1004 to the instrument andfixes the rotational orientation, for example, prevents the camera 1002from rotating relative to the instrument. This may be accomplished byany suitable structure or method, but in some examples, is accomplishedby one or more clips that fix the rotational of the camera 1002 orcamera housing 1004 relative to the probe 500 or optical fiber housing1023. This may also be accomplished by abutting the fiber optic of theinstrument against a flat surface of the sensor array. In someembodiments a fastener 1010 couples the inserter housing 1215 or theoptical fiber housing 1012 to the camera housing 1004 with a fixedangular or rotational orientation. The fastener may comprise anengagement structure which may be a flat surface, a slot, a key, akeyway, a groove, an aperture, a protrusion, a boss, or some othersuitable structure for fixing the orientation of one or more of theoptical fiber housing 1012, the camera housing 1004, or the inserterhousing 1215.

In some embodiments, a fastener 1010 comprises a clip that engages thecamera housing 1004, the inserter housing 1215, or the optical fiberhousing 1012 and in some cases, the clip engages with the camera housing1004, the inserter housing 1215, or the optical fiber housing 1012 toprovide a fixed orientation. Alternatively or in combination, thefastener 1010 comprises an aperture sized and shaped to receive thecamera housing 1004, the inserter housing 1215, or the optical fiberhousing 1012 and to provide a fixed orientation. In some instances, thefastener 1010 allows the camera housing 1004 to slide relative to theinserter housing 1215 or the optical fiber housing 1012.

In some embodiments, the fastener 1010 fixes a distance between thedistal end of the treatment probe 500 and the detector array 1006. Thefastener 1010 may comprise a stop, a pair of stops, an interlockingmechanism, a nesting mechanism, a circumferentially extending channel, acircumferentially extending protrusion, an annular protrusion, anannular recess, or some other suitable structure that provides a stop tolimit the relative distance between the distal end of the probe 500 andthe detector array 1006. In some embodiments, distance between thedistal end of the probe 500 and the detector array are fixed, while inother cases there is relative movement therebetween up to the limitsprovided by the fastener.

FIG. 10 shows a length of the fastener 1010 extending along an elongatedirection of the imaging probe 100 and the treatment probe 500. FIG. 11shows a first direction transverse to the elongate direction of thetreatment probe 500 and the imaging probe 1000. The fastener 1010 can besized and shaped to extend around at least a portion of the camerahousing 1004 and a portion of the inserter housing 1215 as describedherein or the optical fiber housing 1012 as described herein. Thefastener 1010 comprises a first distance 1104 transverse to the camerahousing 1004 and the inserter housing 1215 or the optical fiber housing1012, and a second distance 1106 transverse to the camera housing 1004and the inserter housing 1215 or the optical fiber housing 1012 as shownin FIG. 11. The elongate distance 1011 of the fastener 1010 may comprisea third distance along an elongate axis the camera housing 1004 and theinserter housing 1215 or the optical fiber housing 1012. In someembodiments, the second distance is less than the first distance, andthe third distance is greater than the second distance and the firstdistance. In some embodiments, the first distance is within a range fromabout 1.0 mm to about 2 mm, the second distance within a range fromabout 0.8 to 1.5 mm and the third distance within a range from about 2mm to about 20 mm, for example. In some embodiments these ranges aresmaller, for example the first distance can be within a range from about1.3 to about 1.7 mm, the second distance can be within a range fromabout 1.0 to 1.3 mm, and the third distance within a range from aboutfrom about 2 mm to about 10 mm. The third distance along the elongatedirection can be longer than the first transverse distance and thesecond transverse distance to add stiffness to the coupling between theimaging probe and the treatment probe 500.

With reference to FIGS. 12A and 12B, an example of a treatment probe 500and camera 1002 enclosed within a housing 1202 is shown, in accordancewith some embodiments. The treatment probe 500 comprises an integratedhousing 1202 that encloses an optical fiber and a camera. The camera1002 may comprise a detector array 1006, a lens 1008, and circuitry tocouple the camera 1002 to a controlling unit as described herein. Theintegrated housing 1202 may comprise an aperture 1204 to allow a lens1008 of the camera 1002 to view features of interest. An optical axis1022 extends from the detector array 1006 and through the lens 1008toward the distal end of the probe. The optical fiber 1014 has a distalend that is spaced a distance from the lens 1008, as previouslydescribed.

FIG. 12B is a cross-sectional schematic view of the probe of FIG. 12Ataken along the line B-B. The integrated housing 1202 has a maximumdimension D that is selected to allow insertion of the probe into theeye to access a treatment location, such as within the anterior chamberof a patient's eye. In some embodiments, the maximum dimension D iswithin the range of from about 0.5 mm to about 3 mm, or from about 1 mmto about 2 mm, for example

In some embodiments, the probe comprises a length within a range fromabout 10 mm to about 50 mm sized for insertion into the eye. The lengthof the probe, in some cases, is selected to allow the probe to reach andcompress the trabecular meshwork with the inclined distal end within theeye of a patient.

The optical fiber core 1206 and cladding may be encased by an opticalfiber housing 1012. The optical fiber housing 1012 may comprise anysuitable material, but in some cases is stainless steel. The opticalfiber housing 1012 has a maximum cross-sectional dimension E within therange of from about 300 μm to about 1000 μm. In some embodiments, theoptical fiber housing 1012 has a diameter within a range from about 100μm to about 500 μm, or 150 μm to about 300 μm, and optionally within arange from about 150 μm to about 250 μm. The camera housing 1004 maycomprise a maximum cross-sectional dimension within the range of fromabout 0.8 mm to about 1.2 mm. As shown in FIG. 12B, in some embodiments,the integrated housing 1202 encloses both the camera 1002 and theoptical fiber 1014 and may comprise any suitable cross-sectional shapeand size. In some embodiments, the integrated housing 1202 is sized andshaped to deliver the camera 1002 and optical fiber 1014 to the anteriorchamber of a patient's eye, and more specifically, deliver the opticalfiber 1014 toward the trabecular meshwork to deliver laser energy to thetrabecular meshwork. In some embodiments the optical fiber 1014comprises an inclined distal end to uniformly comprise the trabecularmeshwork to form one or more openings into Schlemm's canal.

FIG. 13 shows a probe 500 comprising an optical axis 1022 inclinedrelative to an elongate axis 1302 of the treatment probe 500. The probe500 may be similar, or identical, to probes shown and described in otherfigures, and may share components with embodiments of probes describedherein. The inclined optical axis 1022 can decrease movement of out offocus tissue as the probe 500 is advanced toward the target location,and may facilitate movement of the treatment probe 500 toward the targettissue. Although the treatment probe 500 is shown having an integratedhousing 1202 that comprises a camera 1002 and an optical fiber 1014, theoptical fiber 1014 and camera 1002 can be coupled to each other with afastener as described herein, so as to incline the optical axis 1022 inrelation to the distal end of the probe 500. The inclined optical axis1022 can be combined with the implant placement devices as describedherein. For example, the optical axis 1022 can be oriented toward thedistal tip of the implant placement probe or the implant on the distalend of the probe.

In some embodiments, a prism 1304 is located along the optical path todeflect the optical axis 1022. The prism 1304 may comprise a discreteoptical element located along the optical path with the lens.Alternatively, the prism 1304 may be located on a surface of the lens.In some embodiments, the lens comprises a wedge in order to deflectlight along the optical path.

In some embodiments, the inclined optical axis 1022 of the camera 1002may allow the camera 1002 to image an implant carried by the integratedhousing 1202 with the implant approximately centered in the cameraimage. Alternatively or in combination, the inclined optical axis 1022may allow the camera 1002 to image the distal tip of the optical fiber1014 approximately centered in the image, to allow the surgeon to usethe distal tip to aim the probe 500 at the treatment site. In someembodiments, the camera 1002 is slidable relative to the integratedhousing 1202, and the optical axis 1022 can thereby be moved, such as topass through the distal tip of the optical fiber 1014 or beyond. Forexample, the imaging probe can be coupled to the treatment probe 500with a slidable fastener as described herein. Alternatively, the camera1002 can be slidable relative to the treatment probe 500 within theintegrated housing 1202.

FIG. 14 shows a method 1500 of treating an eye, in accordance with someembodiments. At a step 1502, a system receives a plurality of cameraimages from a camera inserted in the eye of a patient or in anendoscope. In some embodiments, an endoscope comprising a lens and afiber optic array transmits light captured at the treatment site to adetector array outside the patient that creates images. At a step 1504,user input is received that identifies anatomical locations such as oneor more of ciliary body band, scleral spur, Schwalbe's line, orSchlemm's canal. The user input may be provided by a user such as asurgeon with a touch screen display identifying locations of one or moreof the ciliary body band, the iris root, the scleral spur, Schwalbe'sline or Schlemm's canal. At a step 1506, a classifier or neural networkis trained in response to user input and the plurality of camera images,which may additionally or alternatively comprise endoscope images. Theclassifier or neural network, in some cases, is trained in featurerecognition such that the classifier or neural network can detect andidentify anatomical features within the eye of a patient, such as one ormore of ciliary body band, scleral spur, Schwalbe's line, or Schlemm'scanal, for example. The classifier or neural network may comprise anycombination of suitable image processing algorithms. In someembodiments, the neural network comprises a convolutional neural networkas is known to one of ordinary skill in the art of training neuralnetwork. The classifier may comprise any suitable classifier, such asmachine learning, for example supervised machine learning such asmachine learning with Bayesian statistics, for example random forest asis known to one of ordinary skill on the art. Image processingalgorithms such as edge detection can be used as input to theclassifier. Once the neural network or classifier, or both have beentrained, the trained classifier or neural network can be used toidentify structures of the eye and provide markers as disclosed herein.

At a step 1508, the probe with the camera is placed in an eye to betreated. According to some embodiments, the probe with the cameracomprises an endoscope or a fiberscope to image the eye to be treated.Alternatively to placing the detector array inside the eye, the detectorarray can be located outside the eye as described herein.

At a step 1510, the processor receives images from the camera orendoscope placed in the eye. The images may be acquired at a desiredframerate. In some embodiments, the framerate approximates smoothmotion, such as about 15 fps, 20 fps, 25 fps, 30 fps, or greater.

At a step 1512, anatomical features are identified, such as one or moreof a ciliary body band, scleral spur, Schwalbe's line, or Schlemm'scanal, such as by using a neural network or a classifier.

At a step 1514, a rotation angle of the camera or endoscope relative tothe one or more anatomical features is determined.

At a step 1516, a rotation angle of the probe is determined. In someembodiments, the rotation angle of the probe is fixed with respect tothe rotation angle of the camera or endoscope, and thus determining therotation angle of the camera results in the same rotation angle of theprobe.

At a step 1518, an image of the eye from the interior of the eyeprovided by the endoscope is displayed on a heads up display along withan optical image from an operating microscope. The endoscope maycomprise a camera inserted into the eye, which provides the image, or anendoscope with an external sensor array, which provides the image. Thisimage may be presented as a picture in picture display and may bedisplayed through one or both eyepieces of a microscope. Althoughreference is made to a heads-up display, the display may comprise one ormore of a two-dimensional display, e.g. a monitor, heads-up display ofan operating microscope, an augmented reality display, a virtual realitydisplay, a three-dimensional display, or a stereoscopic image display,e.g. with depth perception.

At a step 1520 a marker is shown on the image from the camera orendoscope placed in the patient. The marker can be overlaid on of one ormore of the ciliary body band, scleral spur, Schwalbe's line, orSchlemm's canal. The one or more markers can be placed on the image usedto identify the tissue structure, or on a subsequent image from thecamera or endoscope inside the eye. In some cases, the markers areoverlaid on the images from the camera or endoscope to present anaugmented image.

At a step 1522, the rotational angle of the camera, the endoscope, orthe probe is shown on the heads-up display. The rotation angle may be anumerical value, one or more lines, or an angle with respect to ahorizontal line, or some other indicia indicating a rotation angle ofthe probe or the camera, for example a green light when the probe isrotationally aligned within an appropriate tolerance, for example towithin 5 degrees.

One or more steps of the method of FIG. 14 may be performed withcircuitry or processor instructions as described herein, for example,one or more of a processor or a logic circuitry of the systems describedherein. The circuitry may be programmed to provide one or more steps,and the program may comprise program instructions stored on a computerreadable memory or programmed steps of the logic circuitry such as withprogrammable array logic or a field programmable gate array, forexample.

Although FIG. 14 shows a method in accordance with some embodiments, aperson of ordinary skill in the art will recognize many variations andadaptations in accordance with the teachings disclosed herein. Forexample, steps of the method can be removed. Additional steps can beprovided. Some of the steps can be repeated. Some of the steps maycomprise sub-steps. Some of the steps can be repeated. The order of thesteps can be changed.

The convolutional neural network may be used to classify image data, andthis, or an alternative machine learning algorithm, may be applied toresult in the generation of markers and other indicia used to augmentimages from an in-situ camera or endoscope, or images from an operatingmicroscope, or both. The result is the generation of augmented imagesthat allow a surgeon to quickly identify anatomical features anddetermine that the probe is properly aligned with the anatomicalfeatures, such as for deploying an implantable device that requiresproper alignment and/or orientation.

With reference to FIG. 15, a system 400 for aiding a physician toperform a surgical procedure on an eye E with an endoscope 1530, isillustrated in accordance with some embodiments. The surgical operationprocedure may comprise inserting an elongate probe 23 from an openinginto the eye across an anterior chamber to a target tissue regioncomprising a trabecular meshwork and a Schlemm's canal. In someembodiments, the system 400 may comprise an optical microscope 409 forthe surgeon to view the eye during the procedure in real-time. Anendoscope input 1501 receives a feed from the endoscope placed in theeye as input. The feed may comprise an optical feed or an electricalfeed, and combinations thereof. In some embodiments, the endoscope iscoupled to the endoscope input 1501 with a flexible cable. The flexiblecable may comprise an ordered array of optical fibers, in which thearrangement of optical fibers is substantially fixed on both ends totransmit an image of the eye to the eye to the endoscope input 1501. Thedistal end of the optical fiber array can be substantially fixed withrespect to a lens that forms and image on the distal end of the opticalfiber array, and the proximal end of the optical fiber array can besubstantially fixed with respect to a detector array that receives theimage from the array of optical fibers. In some embodiments, thesubstantially fixed arrangement on both ends can allow rotation of theprobe while maintaining orientation of the image formed on the distalend of the optical fiber array with respect to the image transmittedfrom the proximal end of the optical fiber array to the detector array.

The endoscope input 1501 is operatively coupled to a processor 414 ofthe control unit 410. The endoscope input 1501 may comprise an inputfrom a sensor of a camera placed in the eye or an external sensor arrayas described herein. The processor 414 of the control unit 410 can beconfigured with instructions to identify locations of structures of theeye and overlay indicia such as markers on the input endoscope images.In conjunction with the optical microscope 409, an endoscope placed inthe eye may provide an endoscope input 1501 to a controlling unit 410.In some embodiments, a camera 416 comprising a detector array isoptically coupled to the optical microscope 409 to receive opticalimages from the operating microscope, and optically coupled to theprocessor of the control unit 410. The control unit 410 can process theimages from the camera 416 and process the images to provide visualimage data on the heads up display 407 to overlay the visual image dataon an anterior optical image of the operating microscope. Althoughreference is made to a heads-up display, the display 407 may compriseone or more of a two-dimensional display, e.g. a monitor, heads-updisplay of an operating microscope, an augmented reality display, avirtual reality display, a three-dimensional display, or a stereoscopicimage display, e.g. with depth perception.

The microscope may comprise a binocular surgical operating microscope,for example. The system 400 may comprise an endoscope 1530 that isdelivered in situ along with the treatment probe 23 to provide imagingof one or more target locations before, during, or after the procedure.The endoscope 1530 of the probe 23 may comprise any suitable imagingdevice, and in some cases, may comprise one or more optical fibers, suchas a fiber optic array. A lens may focus light onto the one or moreoptical fibers which convey the imaging data from within the eye to theendoscope input 1501. A detector array may be positioned within theendoscope input, in a handpiece of the system, or anywhere within thesystem to receive the light conveyed by the one or more optical fibersand convert the light into imaging data. In some embodiments, thedetector array may be a CCD or CMOS imaging sensor located outside theeye of the patient, and may be contained within an endoscope handpiece,in the endoscope input 1501, or within the controlling unit 410. Imagesconveyed by the endoscope and captured by the detector array may beprocessed by an image processing apparatus 412 of the controlling unit410 to generate a plurality of augmented images visualized by thephysician in real time.

The augmented images can be shown on a display of the heads up display407, and combined with optical images from the microscope with aninternal beam splitter 708 to form monocular or binocular images as isknown to one of ordinary skill in the art. As described herein, amicroscope view may comprise one or more of an optical microscope image,an image from an endoscope placed in the eye, a microscope image and anoverlaid virtual image, or a microscope image in combination withimaging captured by the endoscope with or without an overlaid virtualimage, for example. When a microscope view includes an overlaid image,the overlaid image can be registered with the microscope image usingelements which enable such alignment. Similarly, when the view includesimaging from the endoscope and an overlaid virtual image, the overlaidimage can be registered with the imaging from the endoscope usingelements which enable such alignment.

The images can be provided to the surgeon in many ways. For example, thesurgeon can view the images with an augmented reality display such asglasses or goggles and view the surgical site through the operatingmicroscope. In some embodiments, the surgeon views the images withvirtual reality display. Alternatively, or in combination, the eye canbe viewed with an external monitor, and the images of the eye viewedwith the external monitor with markings placed thereon as describedherein. The images viewed by the surgeon may comprise monocular imagesor stereoscopic images, for example.

According to some embodiments, a surgeon may first view a surgicalinstrument, such as a probe, in the microscope or a video image from theoperating microscope. In some cases, the surgeon may alternatively, oradditionally, view images captured by the endoscope showing the probe.According to some embodiments, a surgeon may view images from themicroscope and images captured from the endoscope through the oculars ofthe microscope. Alternatively or in combination, the surgeon may view anaugmented image or view, where additional information is overlaid on oneor more of the optical microscope image or the endoscope image. Whenthere is an image captured by the endoscope overlaid on the image fromthe microscope image, the surgeon can view both the microscope image andconcurrently the overlaid endoscope image. Furthermore, the imageprocessing apparatus 412 can detect anatomical features of the eye asdescribed herein, and overlay markers onto the microscope image or theendoscope image to help guide a surgeon in identifying and locatingthese features. The augmented images may be presented to the physicianthrough an eyepiece (or eyepieces) or oculars of the microscope and/or adisplay of the microscope, and in some embodiments may be viewed on amonitor screen. This may be beneficial to allow a surgeon to maintain astereoscopic view of an operative site through the oculars of themicroscope while simultaneously viewing superimposed or adjacent imagesor information concurrently either stereoscopically or monocularly, forexample. Real-time images captured by the endoscope in situ and realtime treatment information can be superimposed to the live view of oneor both oculars. In some embodiments, the apparatus and methodsdisclosed provide a real-time view including real and augmented imagesfrom both outside and inside of the anterior chamber during thesesurgeries.

The optical microscope 409 may be operatively coupled to an endoscopeinserted into the eye in many ways. The optical microscope 409 maycomprise a binocular microscope such as a stereo-microscope comprisingimaging lens elements to image an object onto an eyepiece(s) comprisingan ocular 408. The endoscope placed in the eye is configured to captureoptical images of the eye. The optical images may be transmitted to thecontrolling unit 410 for processing. The endoscope placed in the eye maycomprise optical elements (e.g., lens, mirrors, filters, prisms, etc.).The endoscope may capture color images, greyscale images and the like,and may be introduced with the probe and moved with the probe, or theprobe may move independently of the endoscope while maintainingrotational alignment with the probe. In some instances, the probe andthe endoscope move together during insertion to a location of interest,and then the probe or the endoscope can move independently of the otherwhile maintaining rotational alignment.

Although reference is made to the endoscope and treatment probe 500inserted through the same incision, in some embodiments the endoscopeand treatment probe 500 are inserted through different incisions withthe endoscope placed to image the target tissues. For example, theimaging probe can be inserted through a first incision and the treatmentprobe 500 inserted through a second incision and vice versa.

The endoscope images may be acquired at an appropriate image frameresolution. The image frame resolution may be defined by the number ofpixels in a frame. The image resolution of the detector that receiveslight transmitted by one or more optical fibers of a fiber optic arrayof the endoscope placed in the eye may comprise any of the followingresolutions: 160×120 pixels, 249×250, 250×250, 320×240 pixels, 420×352pixels, 480×320 pixels, 720×480 pixels, 1280×720 pixels, 1440×1080pixels, 1920×1080 pixels, 2048×1080 pixels, 3840×2160 pixels, 4096×2160pixels, 7680×4320 pixels, or 15360×8640 pixels. The resolution of thearray detector coupled to the endoscope may comprise a resolution withina range defined by any two of the preceding pixel resolutions, forexample within a range from 160×120 pixels to 250×250 pixels, e.g.249×250 pixels. The imaging device may have a pixel size smaller than 1micron, 2 microns, 3 microns, 5 microns, 10 microns, 20 microns and thelike. The detector array may have a footprint on the order of 2 mm×2 mm,or 1 mm×1 mm, 0.8 mm×0.8 mm, or smaller, or any other desirable size todetect light transmitted by the fiber optic array.

The images from the endoscope may comprise a sequence of image framescaptured at a specific capture rate. In some embodiments, the sequenceof images may be captured at standard video frame rates such as about24p, 25p, 30p, 43p, 48p, 50p, 60p, 62p, 72p, 90p, 100p, 120p, 300p, 50ior 60i, or within a range defined by any two of the preceding values. Insome embodiments, the sequence of images may be captured at a rate lessthan or equal to about one image every 0.0001 seconds, 0.0002 seconds,0.0005 seconds, 0.001 seconds, 0.002 seconds, 0.005 seconds, 0.01seconds, 0.02 seconds, 0.05 seconds, or 0.1 seconds. In some cases, thecapture rate may change depending on user input and/or externalconditions under the guidance of the control unit 410 (e.g. illuminationbrightness).

The images captured by the endoscope may be captured in real time, suchthat images are produced with reduced latency, that is, with negligibledelay between the acquisition of data and the rendering of the image.Real time imaging allows a surgeon the perception of smooth motion flowthat is consistent with the surgeon's tactile movement of the surgicalinstruments (e.g. the elongate probe and the probe tip) during surgery.Real time imaging may include producing images at rates faster than 30frames per second (fps) to mimic natural vision with continuity ofmotion, and at twice that rate to avoid flicker (perception of variationin intensity). In some embodiments, the latency may comprise a timeinterval from capturing the images from the endoscope until informationis shown to the user, which may be no more than about 100 ms, forexample 50 ms or less. In some embodiments, the latency comprises nomore than one or two frames of the image shown on the display. In someinstances, the terms “endoscope” and “fiberscope” may be usedinterchangeably. A fiberscope is a flexible optical fiber bundle thatcan be used to view or capture images by transmitting light from adistal end of the optical fiber bundle, through total internalreflection, to a location at a proximal end of the optical fiber bundle.In some instances, a detector array can be positioned at the proximalend of the optical fiber bundle to capture imaging data corresponding toa location near the distal end of the optical fiber bundle. In someinstances, the endoscope may include an imaging bundle, an illuminationbundle, one or more energy delivery bundles, or any combination.

In some embodiments, the optical microscope 409 may be coupled to anelectronic display device 407. The electronic display 407 may comprise aheads-up display device (HUD). The HUD may or may not be a component ofthe microscope system 409. The HUD may be optically coupled into thefield-of-view (POV) of one or both of the oculars. The display devicemay be configured to project augmented images from input 507 generatedby the controlling unit 410 to a user or surgeon. The display device 407may alternatively or additionally be configured to project imagescaptured by the endoscope to a user or surgeon. The display device maybe coupled to the microscope via one or more optical elements such asbeam-splitter or mirror 420 such that a physician looking into theeyepieces 408 can perceive in addition to the real image, endoscopeimaging, augmented images, or any combination represented and presentedby the display device 407. The display device may be visible through asingle ocular to the surgeon or user. Alternatively, the HUD may bevisible through both eyepieces 408 and visible to the surgeon as astereoscopic binocular image combined with the optical image formed withcomponents of the microscope, for example.

The display device of heads up display 407 is in communication with thecontrolling unit 410. The display device may provide augmented imagesproduced by the controlling unit 410 in real-time to a user. Asdescribed herein, real time imaging may comprise capturing the imageswith no substantial latency and allows a surgeon the perception ofsmooth motion flow that is consistent with the surgeon's tactilemovement of the surgical instruments during surgery. In some cases, thedisplay device 407 may receive one or more control signals from thecontrolling unit for adjusting one or more parameters of the displaysuch as brightness, magnification, alignment and the like. The imageviewed by a surgeon or user through the oculars or eyepieces 408 may bea direct optical view of the eye, images displayed on the display 407 ora combination of both. Therefore, adjusting a brightness of the imageson the HUD may affect the view of the surgeon through the oculars. Forinstance, processed information and markers shown on the display 407 canbe balanced with the microscope view of the object. The processor mayprocess the endoscope image data, such as to increase contrast of theimage data so the visible features are more readily detectable oridentifiable.

The heads up display 407 may be, for example, a liquid crystal display(LCD), a LED display, an organic light emitting diode (OLED), a scanninglaser display, a CRT, or the like as is known to one of ordinary skillin the art.

Alternatively or in combination, the display 407 may comprise anexternal display. For example, the display 407 may not be perceivablethrough the oculars in some embodiments. The display 407 may comprise amonitor located in proximity to the optical microscope. The display 407may comprise a display screen, for example. The display 407 may comprisea light-emitting diode (LED) screen, OLED screen, liquid crystal display(LCD) screen, plasma screen, or any other type of screen. The displaydevice 407 may or may not comprise a touchscreen. A surgeon may viewreal-time optical images of the surgical site and imaging provided bythe in-situ endoscope simultaneously from the display 407.

The endoscope inserted into the eye may comprise a fiber optic arraysuitable for capturing imaging at a resolution for viewing tissuestructures of the eye as described herein and may provide images havinga resolution within a range from less than 1 to 10 microns, for examplewithin a range from about 3 to 6 microns, for example. In someembodiments, the endoscope may have a spatial resolution within a rangefrom about 10 μm to about 80 μm for tissue adjacent tissue contactingthe inclined distal end of the probe and optionally wherein theresolution is within a range from about 20 μm to about 40 μm.

In some embodiments, lights that are present for the operatingmicroscope provide sufficient illumination. In some embodiments, theendoscope placed in the eye may optionally comprise a light sourcesuitable for producing images having suitable brightness and focus. Insome embodiments, the endoscope placed in the eye may comprise alight-emitting diode (LED), one or more optical fibers for illuminationsuch as an illumination bundle, or MicroLED. In some embodiments, one ormore color filters can be applied to the imaging captured by theendoscope in order to help isolate, locate, or otherwise identify tissuestructures of interest. The endoscope placed in the eye may be at leastpartially controlled by the controlling unit. Control of the endoscopeby the controlling unit may include, for example, activation of thedetector array for capturing images, controlling illumination,parameters set-up, focus, brightness, contrast, application of one ormore filters, or customizable control parameters.

The endoscope placed in the eye may be coupled to an image sensor havinga high signal to noise ratio. The endoscope may comprise a lens and afiber optic array coupled to a sensor array, or detector array. In someembodiments, one or more lenses of the endoscope comprises borofloatglass, for example. The sensor array may have any suitable number pixelsarranged in a row and column array. In some embodiments, the pixel arraycomprises 249×250 pixels, which may comprise rolling shutter pixels, forexample. In some embodiments, the pixels have a pitch of 3 μm, whichresults in an optical area of 1.06 mm diameter, for example.

The system 400 may further comprise a user interface 413. The userinterface 413 may be configured to receive user input and outputinformation to a user. The user input may be related to control of asurgical tool such as the probe 23. The user input may be related to theoperation of the optical microscope (e.g., microscope settings, imageacquisition, etc.). The user input may be related to various operationsor settings about the image capture system. For instance, the user inputmay include a selection of a target location, a selection of a treatmentreference marker, displaying settings of an augmented image,customizable display preferences and the like. The user interface mayinclude a screen such as a touch screen and any other user interactiveexternal device such as handheld controller, mouse, joystick, keyboard,trackball, touchpad, button, verbal commands, gesture-recognition,attitude sensor, thermal sensor, touch-capacitive sensors, foot switch,or any other device.

In some embodiments, the endoscope placed in the eye is used for guidingthe probe 23 and visualization of the target site. In some embodiments,the endoscope can be configured to view tissue and the probe tip. Insome embodiments, the lens of the endoscope is located at a distance ofabout 10 mm from the probe tip, for example at least about 6 mm from theprobe tip. These distances allow the probe tip to be seen on theendoscope image to target Schlemm's canal.

The controlling unit 410 may be configured to generate an augmentedlayer comprising the augmented information. The augmented layer may be asubstantially transparent image layer comprising one or more graphicalelements. The terms “graphical element” and “graphical visual element”may be used interchangeably throughout this application. The augmentedlayer may be superposed onto the optical view of the microscope, opticalimages or video stream, and/or displayed on the display device. Thetransparency of the augmented layer allows the optical image to beviewed by a user with graphical elements overlay on top of it. In someembodiments, the augmented layer may comprise real time endoscope imagesor other information obtained by one or more of the endoscope placed inthe eye or camera 416.

As described herein, the fusing of the optical microscopic image data,the endoscope image data, the augmented information, or any combination,may comprise incorporating the augmented information into the opticalmicroscopic image or the endoscope image data, or both. The augmentedimage data may comprise one or more graphical elements associated withthe depth information, target location, orientation information, tissueidentification information, or various other supplemental information.The graphical elements may be overlaid onto the optical microscopicimage and/or the endoscope image with a beam splitter 708, for example.A graphical element can be directly overlaid onto an image of any objectvisible in the optical microscopic image. A graphical element may alsoinclude any shape, boundary, or contour surrounding an image of anyobject in the optical microscopic image. The object may be, for example,an instrument inserted into the eye (e.g., probe), a portion of theprobe, target tissues as described herein, and the like.

With reference to FIG. 16 an example treatment probe 500 and endoscope1600 are illustrated in accordance with some embodiments. The endoscope160 is contained within an endoscope housing 1602 and comprises a lens1008 and a fiber optic array 1604. As described elsewhere herein, adetector array that receives light from the fiber optic array 1604 maycomprise an array with any suitable resolution for example of within arange from 200×200 to 300×300 pixels, for example.

A fastener 1010 such as a clip may be used to couple the endoscopehousing 1602 to a treatment optical fiber housing 1012. The treatmentoptical fiber housing 1012 may at least partially enclose a treatmentoptical fiber 1014 configured to delivery light energy to a treatmentsite. The optical fiber housing 1012 and the treatment optical fiber1014 may comprise components of a treatment probe 500 and the endoscopeand endoscope housing 1602 may comprise components of an imaging probe.The optical fiber housing 1012 may be configured with one or morestructures that cooperate with the fastener 1010 to secure the treatmentoptical fiber housing 1012 and the endoscope housing 1602 in a fixedrelative rotational orientation. In other words, the fastener 1010 maysecure the endoscope housing 1602 and the optical fiber housing 1012together such that neither the endoscope housing 1602 or the opticalfiber housing 1012 can rotate substantially about their longitudinalaxes independently of the other, for example no more than about 2degrees. The fastener 1010 may be permanently affixed to either theendoscope housing 1602 or the optical fiber housing 1012 and selectivelyengage the other. Alternatively, the fastener 1010 may comprise aseparate part configured to couple to the treatment probe 500 and theimaging probe 1000.

The distal end 1020 of the treatment probe 500 may be formed with aninclined surface having an angle relative to the longitudinal axis ofthe treatment probe 500. In some embodiments, the distal end of thetreatment probe 500 or the distal end of the treatment optical fiber, orboth, are inclined at an angle α of about 45 degrees to about 65 degreesand optionally at an angle α within a range from about 50 degrees toabout 60 degrees. In some embodiments, the angle α of the distal end ofthe treatment probe 500 is substantially the same as the angle α of thedistal end of the treatment optical fiber. In some embodiments, theangle α of the distal end of the treatment probe 500 is within 10 orfewer degrees of the angle α of the distal end of the optical fiber.

While the illustrated embodiment shows a single treatment optical fiber1014, it should be appreciated that a bundle of treatment optical fiberscould be used with the disclosed systems and methods. In some examples,the treatment probe 500 comprises a bundle of treatment optical fibersthat each have a distal end at or near the angle of the distal end ofthe treatment probe 500.

In some embodiments, the endoscope housing 1602 can translate along itslongitudinal axis in a direction N independently of the treatmentoptical fiber housing 1012. In some cases, the translation distance ofthe endoscope housing 1602 is fixed, such that there are limits to thetranslation distance of the endoscope housing 1602 relative to thetreatment optical fiber housing 1012. In some embodiments, the distalend of the probe 1606 extends beyond the lens 1008 of the endoscope by adistance A within a range from about 2 mm to about 10 mm, or within arange from about 2.5 mm to about 5 mm. In embodiments, in which theendoscope can translate independently of the treatment optical fiberhousing, the translation distance may be bounded by these dimensions,such that the lens of the endoscope can be moved to about 2 mm to about10 mm from the distal end of the optical fiber housing. The travellimits may be provided by any suitable structure or mechanism, such asslots, grooves, protrusions, bosses, stops, and the like.

The treatment probe 500 may be translated in a direction M, and theendoscope housing 1602 may be secured to the treatment probe 500 suchthat the endoscope housing 1602 is translated along with the treatmentprobe 500. In some embodiments, the endoscope housing 1602 mayselectively have a rigid attachment to the optical fiber housing 1012that can be released to provide a degree of freedom for translatingalong its longitudinal axis within translational limits, as describedherein.

In some embodiments, the endoscope 1600 of the imaging probe 1000comprises an optical axis 1022. The optical axis 1022 may extendapproximately parallel to an elongate axis of the treatment opticalfiber 1014, for example parallel to within about 5 degrees. In someembodiments, the treatment optical fiber 1014 comprises an inclineddistal 1020 end as described herein. The imaging fiber optic array 1604may include individual fiber optics that are each aligned with theinclined distal end 1020 of the treatment probe 500, so that the imagesfrom the endoscope 1600 placed in the eye are aligned with the inclineddistal end 1020 of the treatment probe 500. The inclined distal end 1020of the treatment probe 500 may comprise a substantially flat surfacethat defines a surface normal vector 1024. The endoscope 1600 can bepositioned in relation to the surface normal vector 1024 of thetreatment probe 500 in many ways. In some embodiments the surface normalvector 1024 of the treatment probe 500 and the optical axis 1022 of theimaging probe 1000 extend along a common plane. In some embodiments, theinclined distal surface 1020 of the treatment probe 500 faces away fromthe optical axis 1022 of the imaging probe 1000, for example with thesurface normal vector 1024 directed away from the optical axis 1022. Inalternative embodiments, the inclined distal surface 1020 faces towardthe optical axis 1022, for example with the surface normal vector 1024directed toward the optical axis 1022.

In some embodiments, individual fibers of the imaging fiber optic array1604 are aligned with the inclined distal end 1020 of the treatmentprobe 500, such that the imaging fiber optic array 1604 extends in adirection corresponding to the component of the surface normal vector1024 extending away from the elongate axis of the optical fiber.Alternatively, individual fibers of the imaging fiber optic array 1604can be rotated relative to the inclined distal end 1020 of the treatmentfiber, and a processor can be used to rotate the image shown to thesurgeon in order to align the image of the eye from the endoscope placedin the eye with the inclined distal end of the treatment probe 500.Although reference is made to a treatment probe 500 with an opticalfiber 1014, the treatment probe 500 may comprise a probe with implantsas described herein, and the processor used to rotate the image shown tothe surgeon.

In some embodiments, the individual fibers of the imaging fiber opticarray 1604 are constrained in their individual rotation about theirelongate axes. That is, individual fibers are not free to rotate. Thisconstraint may be helpful for forming and capturing images at theproximal end of the fiber optic array 1604. Additionally, in someembodiments, the imaging fiber optic array 1604 as a whole isconstrained from rotating relative to the optical fiber housing 1012,thus helping the imaging provided to the surgeon to represent anaccurate orientation of the endoscope housing 1602 relative to theoptical fiber housing 1012.

FIG. 17 is a cross-sectional schematic view of the probe of FIG. 16taken along the line A-A. The imaging probe may have an endoscope 1600comprising a lens 1008 and a fiber optic array 1604. An endoscopehousing 1602 may comprise one or more optical fibers, such as the fiberoptic array 1604. The treatment optical fiber housing 1012 may beaffixed to the endoscope housing 1602 to prevent independent rotation ofthe endoscope housing 1602 or the optical fiber housing 1012.

According to some embodiments, a fastener 1010 may affix the treatmentoptical fiber housing 1012 to the endoscope housing 1602. The fastener1010 may comprise a clip which may be secured in a longitudinal grooveof the treatment optical fiber housing 1012. In some embodiments, theclip is affixed to the endoscope housing 1602 and comprises anengagement structure such as, for example, a flat engaging surface, aslot, a key, a groove, an aperture, a protrusion, or other suitablestructure. In some embodiments, the clip couples the treatment opticalfiber housing 1012 to the endoscope housing 1602 with a fixed angularorientation.

In some embodiments, the endoscope housing 1602 or the treatment opticalfiber housing 1012, or both, have flat engaging surfaces to provideintimate surface contact between the endoscope housing 1602 and theoptical fiber housing 1012, and to orient the optical fiber housing 1012for receiving the fastener.

In some embodiments, the endoscope housing 1602 has a maximum dimensionD to allow the endoscope housing 1602 the be inserted into the eye of apatient, which may be within the range of about 0.8 mm to about 1.2 mm.The treatment optical fiber housing 1012 may have a maximumcross-sectional dimension E within the range of from about 300 μm toabout 600 μm, and in some embodiments, the dimension E is smaller thanthe dimension D. While the endoscope housing 1602 and the treatmentoptical fiber housing 1012 are represented schematically as having agenerally cylindrical cross section, the respective housings may haveany suitable cross-sectional shape, such as ovoid, hexagonal, octagonal,circular, or any suitable shape.

In some embodiments, the fastener 1010 may comprise a clip or anaperture to engage one or more of the endoscope housing 1602, theinserter housing 1215, or the treatment optical fiber housing 1012 andoptionally the clip comprises the engagement structure sized and shapedto receive the endoscope housing, the inserter housing 1215, the opticalfiber housing, or a combination.

The fastener 1010 may allow the endoscope housing 1602 to slide inrelation to the inserter housing 1215 or the treatment optical fiberhousing 1012 while the rotational orientation of the endoscope 1600 tothe inserter housing 1215 or the optical fiber housing 1012 remainsfixed.

The imaging probe comprising the endoscope 1600 may be fastened to thetreatment probe 500 with the fastener, such that the rotationalorientation of the endoscope relative to the rotational orientation ofthe instrument is fixed, that is, the endoscope 1600 cannotsubstantially rotate independently of the treatment probe 500, e.g. morethan five degrees, for example no more than two degrees, e.g. no morethan one degree. In some embodiments, the rotation orientation is fixedby use of cooperating structures that reduce the likelihood of relativerotation between the endoscope 1600 and the treatment probe 500. In someembodiments, a clip secures the endoscope 1600 to the treatment probe500 and fixes the rotational orientation, for example prevents theendoscope 1600 from rotating relative to the instrument (e.g., thetreatment probe 500). This may be accomplished by any suitable structureor method, but in some examples, is accomplished by one or more clipsthat fix the rotational of the endoscope relative to the probe. This mayalso be accomplished by abutting the fiber optic of the instrumentagainst a flat surface of the endoscope 1600. In some embodiments afastener 1010 couples the inserter housing 1215 or the optical fiberhousing 1012 to the endoscope housing 1602 with a fixed angular orrotational orientation. The fastener 1010 may comprise an engagementstructure which may be a flat surface, a slot, a key, a keyway, agroove, an aperture, a protrusion, a boss, or some other suitablestructure for fixing the orientation of one or more of the opticalfiber, the endoscope, or the inserter housing 1215.

In some embodiments, a fastener 1010 comprises a clip that engages theendoscope housing 1602, the inserter housing 1215, or the treatmentoptical fiber housing 1012 and in some cases, the clip engages with theendoscope housing 1602, the inserter housing 1215, or the optical fiberhousing 1012 to provide a fixed orientation. Alternatively or incombination, the fastener comprises an aperture sized and shaped toreceive the endoscope housing 1602, the inserter housing 1215, or thetreatment optical fiber housing 1012 and to provide a fixed orientation.In some instances, the fastener allows the endoscope housing 1602 toslide relative to the inserter housing 1215 or the optical fiber housing1012.

In some embodiments, the fastener fixes a distance between the distalend of the treatment probe 500 and the lens of the endoscope 1600. Thefastener 1010 may comprise a stop, a pair of stops, an interlockingmechanism, a nesting mechanism, a circumferentially extending channel, acircumferentially extending protrusion, an annular protrusion, anannular recess, or some other suitable structure that provides a stop tolimit the relative distance between the distal end of the probe 1606 andthe lens 1008 of the endoscope. In some embodiments, a distance betweenthe distal end of the probe 1606 and the lens 1008 are fixed, while inother cases there is relative movement therebetween up to the limitsprovided by the fastener.

FIG. 16 shows a length of the fastener extending along an elongatedirection of the imaging probe and the treatment probe 500. FIG. 17shows a first direction transverse to the elongate direction of thetreatment probe 500 and the imaging probe. The fastener can be sized andshaped to extend around at least a portion of the endoscope housing 1602and a portion of the inserter housing 1215 as described herein or thetreatment optical fiber housing 1012 as described herein. The fastener1010 may comprise a first distance transverse to the endoscope housing1602 and the inserter housing 1215 or the optical fiber housing 1012,and a second distance transverse to the endoscope housing and theinserter housing 1215 or the optical fiber housing as shown in FIG. 17.The elongate distance of the fastener may comprise a third distancealong an elongate axis of the endoscope housing 1602 and the inserterhousing 1215 or the optical fiber housing 1012. In some embodiments, thesecond distance is less than the first distance, and the third distanceis greater than the second distance and the first distance. In someembodiments, the first distance is within a range from about 1.0 mm toabout 2 mm, the second distance within a range from about 0.8 to 1.5 mmand the third distance within a range from about 2 mm to about 20 mm,for example. In some embodiments these ranges are smaller, for examplethe first distance can be within a range from about 1.3 to about 1.7 mm,the second distance can be within a range from about 1.0 to 1.3 mm, andthe third distance within a range from about from about 2 mm to about 10mm. The third distance along the elongate direction can be longer thanthe first transverse distance and the second transverse distance to addstiffness to the coupling between the imaging probe and the treatmentprobe 500.

With reference to FIGS. 18A and 18B, an example of a treatment probe 500and endoscope 1600 enclosed within an integrated housing 1202 is shown,in accordance with some embodiments. The treatment probe 500 comprisesan integrated housing 1202 that encloses an optical fiber 1014 and anendoscope 1600. The endoscope 1600 may comprise a lens 1008, a fiberoptic array 1604, a detector array, and circuitry to couple theendoscope 1600 to a controlling unit as described herein. The integratedhousing 1202 may comprise an aperture to allow a lens 1008 of theendoscope 1600 to view features of interest. An optical axis 1022extends through the lens 1008 toward the distal end of the probe 1606.The treatment optical fiber 1014 has a distal end that is spaced adistance from the lens 1008, as described herein.

FIG. 18B is a cross-sectional schematic view of the probe of FIG. 18Ataken along the line B-B. The integrated housing 1202 has a maximumcross-sectional dimension D that is selected to allow insertion of theprobe into the eye to access a treatment location, such as within theanterior chamber of a patient's eye. In some embodiments, the maximumdimension D is within the range of from about 0.5 mm to about 3 mm, orfrom about 1 mm to about 2 mm, for example

In some embodiments, the probe comprises a length within a range fromabout 10 mm to about 50 mm sized for insertion into the eye. The lengthof the probe, in some cases, is selected to allow the probe to reach andcompress the trabecular meshwork with the inclined distal end within theeye of a patient.

The treatment optical fiber core 1206 and cladding may be encased by anoptical fiber housing 1012. The optical fiber housing 1012 may compriseany suitable material, but in some cases is stainless steel. The opticalfiber housing 1012 has a maximum cross-sectional dimension E that may bewithin the range of from about 300 μm to about 600 μm. In someembodiments, the optical fiber housing 1012 has a diameter within arange from about 100 μm to about 300 μm and optionally within a rangefrom about 150 μm to about 250 μm. The endoscope housing 1602 maycomprise a maximum cross-sectional dimension within the range of fromabout 0.8 mm to about 1.2 mm. As shown in FIG. 12B, in some embodiments,the integrated housing 1202 encloses both the endoscope 1600 and thetreatment optical fiber 1014 and may comprise any suitablecross-sectional shape and size. In some embodiments, the integratedhousing 1202 is sized and shaped to deliver the endoscope 1600 andoptical fiber 1014 to the anterior chamber of a patient's eye, and morespecifically, deliver the optical fiber 1014 toward the trabecularmeshwork to deliver laser energy to the trabecular meshwork. In someembodiments the treatment optical fiber 1014 comprises an inclineddistal end 1020 to uniformly comprise the trabecular meshwork to formone or more openings into Schlemm's canal.

FIG. 19 shows a probe comprising an optical axis 1022 inclined relativeto an elongate axis of the treatment probe 500. The inclined opticalaxis 1022 can decrease movement of out of focus tissue as the probe isadvanced toward the target location, and may facilitate movement of thetreatment probe 500 toward the target tissue. Although the treatmentprobe 500 is shown having an integrated housing 1202 that comprises anendoscope 1600 and a treatment optical fiber 1014, the treatment opticalfiber 1014 and endoscope 1600 can be coupled to each other with afastener as described herein, so as to incline the optical axis 1022 inrelation to the distal end of the probe 1606. The inclined optical axis1022 can be combined with the implant placement devices as describedherein. For example, the optical axis 1022 can be oriented toward thedistal tip of the implant placement probe or the implant on the distalend of the probe.

In some embodiments, a prism 1304 is located along the optical path todeflect the optical axis 1022. The prism 1304 may comprise a discreteoptical element located along the optical path with the lens.Alternatively the prism 1304 may be located on a surface of the lens1008. In some embodiments, the lens 1008 comprises a wedge in order todeflect light along the optical path 1022. In some embodiments, the lens1008 comprises an eccentric lens with prism 1304 to deflect the opticalaxis 1022.

In some embodiments, the inclined optical axis 1022 of the lens 1008 mayallow the endoscope 1600 to image an implant carried by the integratedhousing 1202 with the implant approximately centered in the endoscopeimage. Alternatively or in combination, the inclined optical axis 1022may allow the endoscope 1600 to image the distal tip 1606 of thetreatment optical fiber 1014 or its housing approximately to beapproximately centered in the image, in order to allow the surgeon touse the distal tip 1606 to aim the probe at the treatment site. In someembodiments, the endoscope 1600 is slidable relative to the integratedhousing 1202, and the optical axis 1022 can thereby be moved, so as topass through the distal tip 1606 of the optical fiber 1014 or beyond.For example, the imaging probe can be coupled to the treatment probe 500with a slidable fastener as described herein. Alternatively, theendoscope 1600 can be slidable relative to the probe 500 within theintegrated housing.

FIG. 20 shows a probe 500 comprising one or more illumination opticalfibers, comprising an illumination bundle 2000. In some embodiments, theone or more of illumination optical fibers comprises a plurality offiber bundles. For example, a probe may comprise fiber bundlescorresponding to an illumination bundle 2000, a fiber optic array, andan optical fiber. Each of these devices may be formed of one or moreoptical fibers used to transmit light through total internal reflection.The fibers used with any embodiment described herein may individually beformed of any suitable material, such as glass, quartz, fused silica, orplastic for example. The optical fibers may comprise a core surroundedby transparent cladding material with a lower index of refraction andare designed to transmit light that enters one end of the optical fibersto a second end of the fibers. For example, the proximal end of some ofthe fibers may be coupled to a light source and used to provideillumination to the distal end of the treatment probe 500, while otherfibers may be used to transmit light from the treatment site within apatient to a detector array that captures the light and generates adigital image. In some cases, one or more of the optical fibers isconnected to an energy source and may be used to transmit laser energyto the treatment site.

The illumination bundle 2000 may comprise one or more illuminationoptical fibers that are used to deliver light to the treatment site toprovide illumination for imaging purposes. The fiber optic array 1604may comprise one or more optical fibers that are used to transmit lightfrom the treatment site, to a detector array that creates digital imagesof the treatment site which can be provided to a user or surgeon asdescribed herein. A lens 1008 may focus light onto the distal ends ofindividual fibers that make up the fiber optic array 1604. An opticalfiber 1014, or a bundle of optical fibers, may be used to deliverenergy, such as for cutting, resecting, cauterizing, or some otherpurpose at a treatment site. The illumination bundle 2000, fiber opticarray 1604, and optical fiber 1014 may be disposed within a commonhousing and configured to be delivered to a treatment site, such aswithin an eye of a patient.

The illumination bundle 200 may be disposed within a common housing withthe fiber optic array 1604. Alternatively or additionally, theillumination bundle 2000 may be disposed within a common housing withthe optical fiber 1014. In some cases, an illumination bundle 2000 mayprovide illumination from various locations of the treatment probe 500or the imaging probe or both.

A housing as described herein may enclose the treatment optical fiber1004, the endoscope 1600 and the one or more illumination optical fibersand may further fix a rotational orientation between the endoscope 1600,the treatment optical fiber 1004 and the one or more illuminationoptical fibers 2000. The endoscope may include an ordered arrangement ofa bundle of fibers. In some cases, the ordered arrangement of the bundleof fibers is maintained from the distal end of the bundle of fibers tothe proximal end of the bundle of fibers. In some instances, the orderedarrangement remains consistent at the distal end and the proximal end ofthe bundle of fibers, and in some cases, does not maintain the orderedarrangement at a location between the distal end and the proximal end.The ordered arrangement of the bundle of fibers allows light enteringthe distal end of the bundle of fibers to maintain an orientation topreserve an orientation of an image captured at the proximal end of thebundle of fibers, such as by a detector array.

In some embodiments, an imaging system is delivered to a treatment sitewithin a patient, such as within an eye of a patient. The imaging systemmay include components that are disposed within the patient andadditionally or alternatively include components that are outside thepatient. A camera is an example of an imaging system. A camera may bepositioned at a treatment site within a patient as described herein. Anendoscope is another example of an imaging system. Some components ofthe endoscope, such as a lens and a distal end of a fiber bundle, may belocated at a treatment site, while other components of the endoscope,such as a detector array and a proximal end of the fiber bundle, may belocated remotely from the treatment site, such as, for example, outsidethe patent. The imaging system may be coupled to the apparatus for eyesurgery as described herein, which may be a wired or wirelessconnection.

The present disclosure includes the following numbered clauses, whichare part of the present disclosure. Each clause can be combined with oneor more other clauses to the extent that such a combination isconsistent with the teachings disclosed herein.

Clause 1. An apparatus to treat an eye, comprising: a probe sized forinsertion into the eye, the probe comprising a camera comprising a lensand an array detector, the array detector comprising a plurality of rowsand columns; an implant located near a distal end of the probe, theimplant comprising a distal portion sized and shaped for insertion intoSchlemm's canal; and a processor coupled to the array detector, theprocessor configured with instructions to determine a location ofSchlemm's canal in response to an image of one or more of a ciliary bodyband, a scleral spur, or a Schwalbe's line of the eye.

Clause 2. An apparatus to treat an eye, comprising: a probe sized forinsertion into the eye, the probe comprising a camera comprising a lensand an array detector, the array detector comprising a plurality of rowsand columns; an implant located near a distal end of the probe, theimplant comprising a distal portion sized and shaped for insertion intoa Schlemm's canal of the eye, the distal portion extending along anelongate insertion axis, the distal end coupled to the camera with afixed rotational orientation relative to the inclined distal end of thefiber; and a processor coupled to the array detector, the processorconfigured with instructions to determine an angular orientation of theelongate insertion axis in response to an image of one or more of aciliary body band, a scleral spur, or a Schwalbe's line of the eye.

Clause 3. An apparatus to treat an eye, comprising: a probe sized forinsertion into the eye, the probe comprising an optical fiber and acamera, the camera comprising a lens and an array detector, the arraydetector comprising a plurality of rows and columns; and a processorcoupled to the array detector, the processor configured withinstructions to determine a location of Schlemm's canal in response toan image of one or more of a ciliary body band, a scleral spur, or aSchwalbe's line of the eye.

Clause 4. An apparatus to treat an eye, comprising: a laser; a probecomprising a camera and an optical fiber, the camera comprising a lensand an array detector, the array detector comprising a plurality of rowsand columns, the optical fiber coupled to the laser, the optical fibercomprising an inclined distal end and a proximal end, the distal endcoupled to the camera with a fixed rotational orientation relative tothe inclined distal end of the fiber; and a processor coupled to thearray detector, the processor configured with instructions to determinean angular orientation of the inclined distal end of the fiber inresponse to an image of one or more of a ciliary body band, a scleralspur, or a Schwalbe's line of the eye.

Clause 5. The apparatus of any one of clauses 6 or 9, wherein theprocessor is configured to display the angular orientation of theinclined distal end of the fiber in relation to the distal end on aheads up display of an operating microscope.

Clause 6. The apparatus of any one of clauses 6 or 9 wherein the angularorientation of the inclined distal end comprises one or more a rotationangle around an elongate axis of the probe or a rotation angle around anelongate axis of the camera.

Clause 7. The apparatus of any one of clauses 2, 6, 8 or 9, wherein theprocessor is configured with one or more of a convolutional neuralnetwork, a machine learning algorithm or an edge detection algorithm toidentify the one or more of the ciliary body band or the scleral spurand determine the angular orientation.

Clause 8. The apparatus of any one of clauses 2, 6, 8 or 9, wherein theprocessor is configured with instructions to display a boundary of theciliary body band on a display and optionally wherein the boundary ofthe ciliary body band is shown with a plurality of markers located alonga curved line.

Clause 9. The apparatus of any one of clauses 2, 6, 8 or 9, wherein theprocessor is configured with instructions to display a boundary of thescleral spur on a display and optionally wherein the boundary of thescleral spur is shown with a plurality of markers located along a curvedline.

Clause 10. The apparatus of any one of clauses 2, 6, 8 or 9, wherein theimage on the array detector comprises an image of Schwalbe's line andthe processor is configured with instructions to determine a location ofSchwalbe's line in response to the image.

Clause 11. The apparatus of any one of clauses 2, 6, 8 or 9, wherein theimage on the array detector comprises a visible image of Schlemm'scanal, and the processor is configured with instructions to determine alocation of Schlemm's canal in response to the visible image ofSchlemm's canal and optionally wherein the visible image of Schlemm'scanal comprises a contrast of greater than 5 percent (%).

Clause 12. The apparatus of any one of clauses 2, 6, 8 or 9, wherein theprocessor is configured with instructions to determine a location ofSchlemm's canal in response to the one or more of the ciliary body bandor the scleral spur and to display the location on a subsequent imagefrom the detector array.

Clause 13. The apparatus of any one of clauses 2, 6, 8 or 9, wherein theprobe comprises a maximum dimension across within a range from 0.5 mm to3 mm and optionally within a range from 1 mm to 2 mm.

Clause 14. The apparatus of clause 20, wherein the probe comprises themaximum cross-sectional dimension over a longitudinal distance within arange from 10 mm to 50 mm, to access a trabecular meshwork of the eyeand compress the trabecular meshwork with the inclined distal end.

Clause 15. The apparatus of clause 2, further comprising an inserterhousing and a camera housing enclosing the camera with the fixedrotational orientation, the inserter housing enclosing one or more oneor more movable components coupled to the implant.

Clause 16. The apparatus of clause 6, further comprising an inserterhousing and a camera housing enclosing the camera with the fixedrotational orientation, the inserter housing enclosing one or more oneor more movable components coupled to the implant.

Clause 17. The apparatus of clause 8, further comprising an opticalfiber housing enclosing the optical fiber and a camera housing enclosingthe camera with the fixed rotational orientation.

Clause 18. The apparatus of clause 9, further comprising an opticalfiber housing enclosing the optical fiber and a camera housing enclosingthe camera with the fixed rotational orientation.

Clause 19. The apparatus of claim any one of clauses 16, 17, or 18,further comprising a fastener to couple the inserter housing or theoptical fiber housing to the camera housing with the fixed angularorientation structure, wherein the one or more of the fastener, theinserter housing, the optical fiber housing, or the camera housingcomprises an engagement structure to fix the angular orientation andoptionally wherein the structure comprises one or more of flat engagingsurface, a slot, a key, a groove an aperture or a protrusion andoptionally wherein the angular orientation comprises a fixed orientationand the fastener comprises the engagement structure.

Clause 20. The apparatus of clause 19, wherein the fastener comprisesone or more of a clip or an aperture to engage one or more of the camerahousing, the inserter housing, or the optical fiber housing andoptionally wherein the clip comprises the engagement structure sized andshaped to receive the one or more of the camera housing, the inserterhousing, or the optical fiber housing and optionally wherein fastenercomprises the aperture with the aperture sized and shaped to receive theone or more of the camera housing, the inserter housing or the opticalfiber housing with the fixed orientation.

Clause 21. The apparatus of clause 19, wherein the fastener isconfigured to allow the camera housing to slide in relation to theinserter housing or the optical fiber housing while the orientation ofthe of the camera to the inserter housing or the optical fiber housingremains fixed and optionally wherein the engagement structure comprisesone or more elongate engagement structures to maintain the angle whilethe camera housing slides in relation to the inserter housing or theoptical fiber housing and optionally wherein the elongate engagementstructures comprises one or more of one or more axially elongategrooves, one or more axially elongate flat surfaces or one or moreaxially elongate protrusions.

Clause 22. The apparatus of clause 19, wherein the fastener isconfigured to fix a distance between the distal end of the probe and thearray detector and optionally wherein the engagement structure comprisesone or more of a stop, a pair of stops, an interlocking mechanism, anesting mechanism, a circumferentially extending channel, acircumferentially extending protrusion, an annular protrusion or anannular recess.

Clause 23. The apparatus of clause 19, wherein the camera housingcomprises a maximum distance across within a range from about 0.8 to 1.2mm, the optical fiber housing comprises a maximum distance across withina range from about 300 um to about 600 um, the fastener sized and shapedto extend around at least a portion of the camera housing and a portionof the inserter housing or the optical fiber housing, wherein thefastener comprises a first distance transverse to the camera housing andthe inserter housing or the optical fiber housing, a second distancetransverse to the camera housing and the inserter housing or the opticalfiber housing, and a third distance along an elongate axis the camerahousing and the inserter housing or the optical fiber housing, thesecond distance less than the first distance, the third distance greaterthan the second distance and the first distance.

Clause 24. The apparatus of clause 23, wherein the first distance withina range from about 1.0 mm to about 2 mm, the second distance within arange from about 0.8 to 1.5 mm, the third distance within a range fromabout 2 mm to about 20 mm, the first distance optionally within a rangefrom about 1.3 to about 1.7 mm, the second distance optionally within arange from about 1.0 to 1.3 mm, the third distance optionally within arange from about from about 2 mm to about 10 mm.

Clause 25. The apparatus of clause 9, further comprising a housing toenclose the optical fiber and the camera, the housing comprising aninclined distal end.

Clause 26. The apparatus of clause 25, wherein the inclined distal endof the housing extends circumferentially around at least a portion ofthe inclined distal end of the optical fiber.

Clause 27. The apparatus of clause 25, wherein the inclined distal endof the housing and the inclined distal end of the optical fiber areinclined at an angle to within about 10 degrees of each other andoptionally wherein the inclined distal ends comprise flush surfaces.

Clause 28. The apparatus of clause 25, wherein the detector arraycomprises a side with a flat edge, and the optical fiber extends alongthe side with flat edge of the detector array.

Clause 29. The apparatus of any one of the preceding clauses, whereinthe array detector comprises a number of pixels along a column within arange from about 200 pixels to about 500 pixels and a plurality ofpixels along a row within a range from about 200 pixels to about 500pixels and optionally wherein the number of pixels along the row iswithin a range from about 200 to 300 pixels and the number of pixelsalong the column is within a range from about 200 pixels to about 300pixels.

Clause 30. The apparatus of anyone of the preceding clauses wherein thecamera provides a spatial resolution within a range from about 10 um toabout 80 um for tissue adjacent tissue contacting the inclined distalend of the probe and optionally wherein the resolution is within a rangefrom about 20 um to about 40 um.

Clause 31. The apparatus of claim anyone of the preceding clauses,wherein the distal end of the probe extends beyond a distal most lens ofthe camera by a distance within a range from about 2 mm to about 10 mmand optionally within a range from about 2.5 mm to about 5 mm.

Clause 32. The apparatus of claim anyone of the preceding clauses,wherein the distal end of the probe extends beyond a distal most lens ofthe camera by a distance within a range from about 2 mm to about 10 mmand optionally within a range from about 2.5 mm to about 5 mm andoptionally wherein the distance is dimensioned to visualize a portion ofthe distal end of the probe in the image of the one or more of ciliarybody band or the scleral spur.

Clause 33. The apparatus of claim anyone of the preceding clauses,wherein the array detector is located a distance from the distal end ofthe probe, the distance within a range from about 2.5 mm to about 10.5mm and optionally within a range from about 3 mm to about 6 mm.

Clause 34. The apparatus of claim any one of the preceding clauses,wherein the inclined end comprises an inclined surface to contact atrabecular meshwork of the eye, and wherein the inclined end comprises asurface normal vector pointing in a direction away from the camera andwherein one or more of the rows or the columns is aligned with atransverse component of the surface normal vector to within about 5degrees and optionally wherein the transverse component of the surfacenormal vector extends in a direction transverse to the optical fiber.

Clause 35. The apparatus of claim any one of the preceding clauses,wherein the optical fiber comprises an elongate axis of the opticalfiber, the elongate axis extending along a direction of lightpropagation along the optical fiber, and wherein the inclined distal endtraverses the axis at an angle within a range from about 45 degrees toabout 65 degrees an optionally wherein the angle is within a range fromabout 50 degrees to about 60 degrees.

Clause 36. The apparatus of any one of the preceding clauses, furthercomprising a rotational angle between the distal end of the probe andone or more of the rows or columns of the detector array and wherein theprocessor is configured with instructions to determine the angle betweenthe elongate insertion axis or the inclined end of the fiber and the oneor more of the ciliary body band or the scleral spur in response theimage of one or more of a ciliary body band, a scleral spur, or aSchwalbe's line of the eye and the rotational angle.

Clause 37. The apparatus of any one of the preceding clauses, whereinthe processor is configured with instructions to determine a rotationalorientation angle between the elongate insertion axis or the inclineddistal end of the optical fiber and one or more of the rows or columnsof the detector array.

Clause 38. The apparatus of claim any one of the preceding clauses,wherein the optical fiber comprises a core and a cladding, the claddingcomprising a diameter within a range from about 100 micrometers (um) toabout 300 um and optionally within a range from about 150 um to about250 um.

Clause 39. The apparatus of claim any one of the preceding clauses,wherein the optical fiber comprises a plurality of optical fibers, eachcomprising an inclined distal end, the distal ends aligned to engagetissue of the eye with similar angles to within about 10 degrees.

Clause 40. The apparatus of any one of the preceding clauses, furthercomprising an operating microscope to view an anterior portion of theeye from outside the eye, the operating microscope comprising aplurality of oculars for a user to view an optical image the anteriorportion of the eye formed with a plurality of lenses, the operatingmicroscope comprising a heads-up display to show the image from thecamera when the camera has been place inside the eye in order for theuser to view the anterior image of the eye through the operating andview the image of the eye from the camera in real time, and optionallywherein the image from the camera comprises one or more markers showingthe location of the one or more of the ciliary body band, the scleralspur or Schlemm's canal.

Clause 41. The apparatus of any one of the preceding clauses, furthercomprising an operating microscope to view an anterior portion of theeye from outside the eye, the operating microscope comprising aplurality of oculars for a user to view an optical image the anteriorportion of the eye formed with a plurality of lenses, the operatingmicroscope comprising a heads-up display to show the image from thecamera when the camera has been place inside the eye in order for theuser to view the anterior image of the eye through the operating andview the image of the eye from the camera in real time, and optionallywherein the image from the camera on the heads-up display comprises animage of the implant.

Clause 42. The apparatus of claim any one of the preceding clauses,wherein the camera comprises an optical axis, the optical axis of thecamera aligned with a tissue engaging structure on the probe to withinabout 5 degrees, wherein the tissue engaging structure comprises one ormore of a distal end of a probe shaped to contact the trabecularmeshwork, an inclined distal end of a probe shaped to contact thetrabecular meshwork, a stylet sized and shaped to penetrate thetrabecular meshwork, a tip of the stylet, an implant on the distal endof the probe, or a sharp end of an implant on the distal end of theprobe.

Clause 43. An apparatus of any one of the preceding clauses, wherein animaging system (e.g., camera, scope, probe, fiber, etc.) is configuredto display an image of the anatomy of an interior of an eye and of aprobe located within the interior of the eye, and is further configuredto provide updated images concurrent with movement of the probe.

As detailed above, the computing devices and systems described and/orillustrated herein broadly represent any type or form of computingdevice or system capable of executing computer-readable instructions,such as those contained within the modules described herein. In theirmost basic configuration, these computing device(s) may each comprise atleast one memory device and at least one physical processor.

The term “memory” or “memory device,” as used herein, generallyrepresents any type or form of volatile or non-volatile storage deviceor medium capable of storing data and/or computer-readable instructions.In one example, a memory device may store, load, and/or maintain one ormore of the modules described herein. Examples of memory devicescomprise, without limitation, Random Access Memory (RAM), Read OnlyMemory (ROM), flash memory, Hard Disk Drives (HDDs), Solid-State Drives(SSDs), optical disk drives, caches, variations or combinations of oneor more of the same, or any other suitable storage memory.

In addition, the term “processor” or “physical processor,” as usedherein, generally refers to any type or form of hardware-implementedprocessing unit capable of interpreting and/or executingcomputer-readable instructions. In one example, a physical processor mayaccess and/or modify one or more modules stored in the above-describedmemory device. Examples of physical processors comprise, withoutlimitation, microprocessors, microcontrollers, Central Processing Units(CPUs), Field-Programmable Gate Arrays (FPGAs) that implement softcoreprocessors, Application-Specific Integrated Circuits (ASICs), portionsof one or more of the same, variations or combinations of one or more ofthe same, or any other suitable physical processor.

Although illustrated as separate elements, the method steps describedand/or illustrated herein may represent portions of a singleapplication. In addition, in some embodiments one or more of these stepsmay represent or correspond to one or more software applications orprograms that, when executed by a computing device, may cause thecomputing device to perform one or more tasks, such as the method step.

In addition, one or more of the devices described herein may transformdata, physical devices, and/or representations of physical devices fromone form to another. For example, one or more of the devices recitedherein may receive image data of a sample to be transformed, transformthe image data, output a result of the transformation to determine aprocess, use the result of the transformation to perform the process,and store the result of the transformation to produce an output image ofthe sample. Additionally or alternatively, one or more of the modulesrecited herein may transform a processor, volatile memory, non-volatilememory, and/or any other portion of a physical computing device from oneform of computing device to another form of computing device byexecuting on the computing device, storing data on the computing device,and/or otherwise interacting with the computing device.

The term “computer-readable medium,” as used herein, generally refers toany form of device, carrier, or medium capable of storing or carryingcomputer-readable instructions. Examples of computer-readable mediacomprise, without limitation, transmission-type media, such as carrierwaves, and non-transitory-type media, such as magnetic-storage media(e.g., hard disk drives, tape drives, and floppy disks), optical-storagemedia (e.g., Compact Disks (CDs), Digital Video Disks (DVDs), andBLU-RAY disks), electronic-storage media (e.g., solid-state drives andflash media), and other distribution systems.

A person of ordinary skill in the art will recognize that any process ormethod disclosed herein can be modified in many ways. The processparameters and sequence of the steps described and/or illustrated hereinare given by way of example only and can be varied as desired. Forexample, while the steps illustrated and/or described herein may beshown or discussed in a particular order, these steps do not necessarilyneed to be performed in the order illustrated or discussed.

The various exemplary methods described and/or illustrated herein mayalso omit one or more of the steps described or illustrated herein orcomprise additional steps in addition to those disclosed. Further, astep of any method as disclosed herein can be combined with any one ormore steps of any other method as disclosed herein.

A processor as described herein can be configured to perform one or moresteps of any method described herein.

Unless otherwise noted, the terms “connected to” and “coupled to” (andtheir derivatives), as used in the specification and claims, are to beconstrued as permitting both direct and indirect (i.e., via otherelements or components) connection. In addition, the terms “a” or “an,”as used in the specification and claims, are to be construed as meaning“at least one of.” Finally, for ease of use, the terms “including” and“having” (and their derivatives), as used in the specification andclaims, are interchangeable with and shall have the same meaning as theword “comprising.

The processor as disclosed herein can be configured with instructions toperform any one or more steps of any method as disclosed herein.

It will be understood that although the terms “first,” “second,”“third”, etc. may be used herein to describe various layers, elements,components, regions or sections without referring to any particularorder or sequence of events. These terms are merely used to distinguishone layer, element, component, region or section from another layer,element, component, region or section. A first layer, element,component, region or section as described herein could be referred to asa second layer, element, component, region or section without departingfrom the teachings of the present disclosure.

As used herein, the term “or” is used inclusively to refer items in thealternative and in combination.

As used herein, characters such as numerals refer to like elements.

Although reference is made to an imaging probe comprising a plurality ofoptical fibers, in some embodiments the imaging probe comprises a singleoptical fiber. For example, the imaging probe may comprise a singleoptical fiber configured to deflect with a scan pattern to image lightfrom the eye. The optical fiber can be configured to transmit light to aplurality of locations to generate the internal image of the eye, orconfigured to deflect and receive light from a plurality of locations.

Embodiments of the present disclosure have been shown and described asset forth herein and are provided by way of example only. One ofordinary skill in the art will recognize numerous adaptations, changes,variations and substitutions without departing from the scope of thepresent disclosure. Several alternatives and combinations of theembodiments disclosed herein may be utilized without departing from thescope of the present disclosure and the inventions disclosed herein.Therefore, the scope of the presently disclosed inventions shall bedefined solely by the scope of the appended claims and the equivalentsthereof.

What is claimed is:
 1. A method, comprising: inserting a probe into aneye of a patient; capturing one or more images of an interior of theeye; and determining a location of one or more of a Schlemm's canal or atrabecular meshwork, the one or more images updating concurrent withmovement of the probe, wherein determining the location of Schlemm'scanal is performed by a processor configured with instructions todetermine the location of Schlemm's canal, the image updating concurrentwith movement of the probe.
 2. The method of claim 1, further comprisingdelivering, with the probe, an implant to Schlemm's canal.
 3. The methodof claim 1, further comprising displaying a boundary of a scleral spuron a display and optionally wherein the boundary of the scleral spur isshown by displaying a plurality of markers located along a curved line.4. The method of claim 1, further comprising displaying a boundary of aSchwalbe's line on a display and optionally wherein the boundary of theSchwalbe's line is shown by displaying a plurality of markers atlocations corresponding to the boundary of the Schwalbe's line.
 5. Themethod of claim 1, further comprising delivering laser energy by a laserthrough a treatment optical fiber carried by the probe.
 6. The method ofclaim 1, further comprising overlaying markers onto the one or moreimages of the interior of the eye.
 7. The method of claim 1, furthercomprising contacting a trabecular meshwork of the eye with an end ofthe probe.
 8. The method of claim 1, wherein the one or more images ofthe interior of the eye are captured by a camera coupled to the probe.9. The method of claim 1, wherein the one or more images of the interiorof the eye are captured by an endoscope coupled to the probe.
 10. Themethod of claim 1, wherein the one or more images of the interior of theeye are captured by an external sensor array located outside the eye.